FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Gene: Dmel\E(z)
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General Information
Symbol
Dmel\E(z)
Species
D. melanogaster
Name
Enhancer of zeste
Annotation Symbol
CG6502
Feature Type
FlyBase ID
FBgn0000629
Gene Model Status
Stock Availability
Gene Summary
Enhancer of zeste (E(z)) encodes the catalytic component of the Polycomb Repressive Complex 2 (PRC2) methyltransferase that methylates histone H3 lysine27. Together with PRC1, PRC2 silences developmental genes to determine specific differentiated cell identities. [Date last reviewed: 2019-09-26] (FlyBase Gene Snapshot)
Also Known As

EZ, pco, l(3)1902, Su(z)301, polycombeotic

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
3-33
RefSeq locus
NT_037436 REGION:10634575..10638130
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (22 terms)
Molecular Function (8 terms)
Terms Based on Experimental Evidence (6 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from physical interaction with UniProtKB:Q24459
inferred from physical interaction with UniProtKB:P26017,UniProtKB:Q9XZ06
inferred from physical interaction with UniProtKB:P41046
inferred from direct assay
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000768863
enables DNA binding
non-traceable author statement
inferred from electronic annotation with InterPro:IPR044439
inferred from biological aspect of ancestor with PANTHER:PTN000768863
Biological Process (10 terms)
Terms Based on Experimental Evidence (8 terms)
CV Term
Evidence
References
inferred from mutant phenotype
involved_in axon guidance
inferred from mutant phenotype
involved_in neurogenesis
inferred from mutant phenotype
inferred from genetic interaction with UniProtKB:M9PF84
inferred from mutant phenotype
inferred from mutant phenotype
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
inferred from electronic annotation with InterPro:IPR045318
inferred by curator from GO:0035098
inferred by curator from GO:0046976
inferred by curator from GO:0046974
inferred from biological aspect of ancestor with PANTHER:PTN000768863
Cellular Component (4 terms)
Terms Based on Experimental Evidence (3 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
located_in chromatin
non-traceable author statement
inferred from biological aspect of ancestor with PANTHER:PTN002907402
is_active_in nucleus
inferred from biological aspect of ancestor with PANTHER:PTN000768863
Protein Family (UniProt)
Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. EZ subfamily. (P42124)
Catalytic Activity (EC/Rhea)
histone methyltransferase activity
protein-lysine N-methyltransferase activity
Summaries
Gene Snapshot
Enhancer of zeste (E(z)) encodes the catalytic component of the Polycomb Repressive Complex 2 (PRC2) methyltransferase that methylates histone H3 lysine27. Together with PRC1, PRC2 silences developmental genes to determine specific differentiated cell identities. [Date last reviewed: 2019-09-26]
Gene Group (FlyBase)
POLYCOMB REPRESSIVE COMPLEX 2, PCL VARIANT -
The Polycomb repressive complex 2 (PRC2) is a Polycomb group complex. Histone-lysine N-methyltransferase which trimethylates catalyzes the trimethylation of K27 of histone H3 (H3K27me3) which serves to recruit PRC1 and K9 of histone H3 (H3K9me3) and promotes heterochromatin formation. The PRC2 core may preferentially interact with Pcl or Jarid2 giving rise to variants. (Adapted from FBrf0188105 & FBrf0252799).
SET DOMAIN LYSINE METHYLTRANSFERASES -
SET domain lysine methyltransferases (KMTs) catalyze the addition of methyl groups to lysine residues. SET domain KMTs possess a domain that was original characterized in the D.mel KMTs Su(var)3-9, E(z) and trx. (Adapted from FBrf0216343).
SANT-MYB DOMAIN TRANSCRIPTION REGULATORS -
The SANT-MYB domain transcription regulators are essentially part of chromatin remodelling complexes and co-repressors. The SANT domain shows similarity with DNA-binding helix-turn-helix of Myb domain, and are involved in protein-protein interactions in the chromatin complexes. (Adapted from PMID:15040448).
POLYCOMB REPRESSIVE COMPLEX 2, JARID2-JING VARIANT -
The Polycomb repressive complex 2 (PRC2) is a Polycomb group complex. Histone-lysine N-methyltransferase which trimethylates catalyzes the trimethylation of K27 of histone H3 (H3K27me3) which serves to recruit PRC1 and K9 of histone H3 (H3K9me3) and promotes heterochromatin formation. he PRC2 core may preferentially interact with Pcl or Jarid2 giving rise to variants. (Adapted from FBrf0188105 & FBrf0252799).
Protein Function (UniProtKB)
Polycomb group (PcG) protein. Catalytic subunit of the Esc/E(z) complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene (PubMed:22354997). As part of the PRC2 complex methylates the PRC2 accessory protein Jarid2 on 'Lys-46' (PubMed:25620564). While PcG proteins are generally required to maintain the transcriptionally repressive state of homeotic genes throughout development, this protein is specifically required during the first 6 hours of embryogenesis to establish the repressed state. The Esc/E(z) complex is necessary but not sufficient for the repression of homeotic target genes, suggesting that the recruitment of the distinct PRC1 complex is also required. Required for recruitment of the PRC2 complex to chromatin and H3K27me3 histone modification (PubMed:22354997).
(UniProt, P42124)
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
E(z): Enhancer of zeste
Locus named after original gain-of-function allele E(z)1 (Kalisch and Rasmuson); subsequently designated polycombeotic (pco) (by Phillips and Shearn) based on phenotype of lethal homozygotes. Loss of function alleles recovered as (a) recessive lethal mutations (b) reversions of E(z)1 and (c) reversions of the antimorphic allele, E(z)59. Reduction of E(z)+ activity leads to suppression of the z eye color, whereas gain-of-function alleles are dominant enhancers of zeste eye color [i.e., z w+/Y; E(z)1/+ males have brownish eyes as do z w+/z+ w+; E(z)1/+ females]. E(z)59 an antimorphic allele, is a dominant suppressor of z [i.e. z w+; E(z)59/+ females have orange eyes]. Hemizygosity for E(z)+ produces a very mild suppression of the z eye color. No effects on eye color in z+ or za backgrounds, and effects on eye color not specific to a particular w allele. Reduction of E(z)+ activity also allows ectopic expression of the segment identity genes of the Antennapedia and bithorax gene complexes, resulting in homeotic transformations. This latter effect defines E(z) as a Polycomb-group locus. E(z)61 displays temperature-sensititive suppression of z eye color and homeotic phenotypes. At 22, z wis/Y; E(z)61/Df(3L)E(z)-males have orange eyes and no homeotic transformations. At 29, such males have wild-type red eyes and die as pharate adults with strong homeotic transformations of the mesothoracic and metathoracic legs toward the prothoracic state. Embryos produced by E(z)61 homozygous females at 29C die with homeotic transformations of most segments toward the eighth abdominal segment. Even two copies of paternally contributed E(z)+ does not rescue viability of these embryos. Complete lack of zygotically produced E(z)+ results in early pupal lethality and small imaginal disks. Larval brain squashes from individuals homozygous for an amorphic allele reveal a very low mitotic index; metaphase chromosomes irregularly condensed and fragmented (Gatti and Baker, 1989, Genes Dev. 3: 438-53).
Summary (Interactive Fly)

transcription factor - polycomb group with trithorax homology - chromatin associated - catalytic component of the Polycomb Repressive Complex 2 (PRC2) methyltransferase that methylates histone H3 lysine27 -together with PRC1, PRC2 silences developmental genes to determine specific differentiated cell identities

Gene Model and Products
Number of Transcripts
3
Number of Unique Polypeptides
2

Please see the JBrowse view of Dmel\E(z) for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Structure
Protein 3D structure   (Predicted by AlphaFold)   (AlphaFold entry P42124)

If you don't see a structure in the viewer, refresh your browser.
Model Confidence:
  • Very high (pLDDT > 90)
  • Confident (90 > pLDDT > 70)
  • Low (70 > pLDDT > 50)
  • Very low (pLDDT < 50)

AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.

Experimentally Determined Structures
Crossreferences
Comments on Gene Model

Gene model reviewed during 5.46

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0076279
2650
760
FBtr0273338
2464
760
FBtr0334067
2479
765
Additional Transcript Data and Comments
Reported size (kB)

3.3, 2.5 (northern blot)

2.5 (northern blot)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0076008
86.9
760
6.29
FBpp0271846
86.9
760
6.29
FBpp0306192
87.5
765
6.37
Polypeptides with Identical Sequences

The group(s) of polypeptides indicated below share identical sequence to each other.

760 aa isoforms: E(z)-PA, E(z)-PB
Additional Polypeptide Data and Comments
Reported size (kDa)

89 (kD observed)

760 (aa); 87 (kD predicted)

Comments

E(z) protein was found to bind to 44 identified sites along the polytene chromosomes.

External Data
Subunit Structure (UniProtKB)

Component of the polycomb repressive complex 2 (PRC2, also known as the Esc/E(Z) complex), composed of Caf1-55, esc, E(z), Su(z)12, and possibly pho (PubMed:11124122, PubMed:11581156, PubMed:12408863, PubMed:12408864, PubMed:9566901). PRC2 associates with the accessory components Jarid2 and jing to form the PRC2 Jarid2-jing variant (PRC2.2) (PubMed:22354997). PRC2 may also associate with Pcl and HDAC1/Rpd3 during early embryogenesis (PubMed:11124122, PubMed:11581156, PubMed:12408863, PubMed:12408864, PubMed:12533794, PubMed:12697833). This complex is distinct from the PRC1 complex, which contains many other PcG proteins like Pc, Ph, Psc, Su(z)2 (PubMed:12533794). The two complexes however cooperate and interact together during the first 3 hours of development to establish PcG silencing. Interacts with corto in vitro (PubMed:12771214).

(UniProt, P42124)
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\E(z) using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Expression Data
Testis-specificity index

The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).

-0.64

Transcript Expression
Polypeptide Expression
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

Abundant E(z) protein is observed in male germline stem cells, gonialblasts, spermatogonia, and very early spermatocytes. Protein levels drop abruptly in spermatocytes in early G2 of meiotic prophase.

E(z) protein is uniformly distributed in embryos. It is ubiquitously distributed in larvae at lower levels.

Marker for
 
Subcellular Localization
CV Term
Evidence
References
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\E(z) in JBrowse
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
FlyExpress - Embryonic expression images (BDGP data)
  • Stages(s) 1-3
  • Stages(s) 4-6
  • Stages(s) 11-12
  • Stages(s) 13-16
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 104 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 29 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of E(z)
Transgenic constructs containing regulatory region of E(z)
Aberrations (Deficiencies and Duplications) ( 8 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Sterility
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
dendrite & dorsal multidendritic neuron ddaC | somatic clone
larval brain & mitosis & nuclear chromosome
mesothoracic leg & sex comb | ectopic
metaphase & condensed chromosome & embryo
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (21)
13 of 14
Yes
Yes
1  
12 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1  
1 of 14
No
No
1 of 14
No
No
3  
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1  
1 of 14
No
No
1 of 14
No
No
1  
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
1  
1 of 14
No
No
1 of 14
No
No
4  
1 of 14
No
No
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (18)
13 of 14
Yes
Yes
12 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Mus musculus (laboratory mouse) (18)
12 of 14
Yes
Yes
12 of 14
Yes
Yes
2 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Xenopus tropicalis (Western clawed frog) (12)
11 of 13
Yes
Yes
6 of 13
No
Yes
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
Danio rerio (Zebrafish) (24)
13 of 14
Yes
Yes
12 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Caenorhabditis elegans (Nematode, roundworm) (20)
10 of 14
Yes
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Anopheles gambiae (African malaria mosquito) (12)
12 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (28)
10 of 13
Yes
Yes
10 of 13
Yes
Yes
10 of 13
Yes
Yes
3 of 13
No
No
2 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
Saccharomyces cerevisiae (Brewer's yeast) (2)
2 of 13
Yes
No
1 of 13
No
No
Schizosaccharomyces pombe (Fission yeast) (3)
2 of 12
Yes
No
1 of 12
No
No
1 of 12
No
No
Escherichia coli (enterobacterium) (0)
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:E(z). Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Drosophila melanogaster (Fruit fly) (10)
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
1 of 13
Human Disease Associations
FlyBase Human Disease Model Reports
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 2 )
Potential Models Based on Orthology ( 1 )
Modifiers Based on Experimental Evidence ( 6 )
Disease Associations of Human Orthologs (via DIOPT v9.1 and OMIM)
Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
Functional Complementation Data
Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
Interactions
Summary of Physical Interactions
Interaction Browsers

Please see the Physical Interaction reports below for full details
protein-protein
Physical Interaction
Assay
References
RNA-protein
Physical Interaction
Assay
References
Summary of Genetic Interactions
Interaction Browsers

Please look at the allele data for full details of the genetic interactions
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
External Data
Subunit Structure (UniProtKB)
Component of the polycomb repressive complex 2 (PRC2, also known as the Esc/E(Z) complex), composed of Caf1-55, esc, E(z), Su(z)12, and possibly pho (PubMed:11124122, PubMed:11581156, PubMed:12408863, PubMed:12408864, PubMed:9566901). PRC2 associates with the accessory components Jarid2 and jing to form the PRC2 Jarid2-jing variant (PRC2.2) (PubMed:22354997). PRC2 may also associate with Pcl and HDAC1/Rpd3 during early embryogenesis (PubMed:11124122, PubMed:11581156, PubMed:12408863, PubMed:12408864, PubMed:12533794, PubMed:12697833). This complex is distinct from the PRC1 complex, which contains many other PcG proteins like Pc, Ph, Psc, Su(z)2 (PubMed:12533794). The two complexes however cooperate and interact together during the first 3 hours of development to establish PcG silencing. Interacts with corto in vitro (PubMed:12771214).
(UniProt, P42124 )
Linkouts
BioGRID - A database of protein and genetic interactions.
DroID - A comprehensive database of gene and protein interactions.
MIST (genetic) - An integrated Molecular Interaction Database
MIST (protein-protein) - An integrated Molecular Interaction Database
Pathways
Signaling Pathways (FlyBase)
Metabolic Pathways
FlyBase
External Links
KEGG Metabolic Pathways - A collection of manually drawn metabolic pathway maps representing knowledge of molecular interaction, reaction and relation networks.
External Data
Linkouts
KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
SignaLink - A signaling pathway resource with multi-layered regulatory networks.
Class of Gene
Genomic Location and Detailed Mapping Data
Chromosome (arm)
3L
Recombination map
3-33
Cytogenetic map
Sequence location
FlyBase Computed Cytological Location
Cytogenetic map
Evidence for location
67E5-67E5
Limits computationally determined from genome sequence between P{lacW}l(3)L0539L0539&P{PZ}Dhh1rL562 and P{PZ}simj01814
Experimentally Determined Cytological Location
Cytogenetic map
Notes
References
67E3-67E4
(determined by in situ hybridisation)
Experimentally Determined Recombination Data
Location

3-34.25 +/- 0.5

3-30.9 +/- 0.7

3-34.0

Left of (cM)
Right of (cM)
Notes

Genetic map position contradicts cytological map position.

Stocks and Reagents
Stocks (20)
Genomic Clones (17)
 

Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete

cDNA Clones (36)
 

Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see JBrowse for alignment of the cDNAs and ESTs to the gene model.

cDNA clones, fully sequenced
BDGP DGC clones
Other clones
Drosophila Genomics Resource Center cDNA clones

For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

cDNA Clones, End Sequenced (ESTs)
RNAi and Array Information
Linkouts
DRSC - Results frm RNAi screens
Antibody Information
Cell Line Information
Publicly Available Cell Lines
 
    Other Stable Cell Lines
     
      Other Comments

      DNA-protein interactions: genome-wide binding profile assayed for E(z) protein in Kc167 cells; see Chromatin_types_NKI collection report. Individual protein-binding experiments listed under "Samples" at GEO_GSE22069 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22069).

      E(z) is required for normal neuroblast proliferation in postembryonic central nervous system development.

      dsRNA has been made from templates generated with primers directed against this gene. RNAi of E(z) causes an increase in branch number and an expansion of the receptive field of class I neurons. RNAi also causes defects in muscle, defects in dendrite morphogenesis and reproducible defects in da dendrite development.

      E(z) is a Polycomb group protein.

      esc protein, together with that of E(z), is present in a 600kD complex that is distinct from complexes containing other PcG proteins. The complex also includes the Rpd3 and Caf1 proteins.

      Evidence of physical interaction between esc and E(z) in vitro and in vivo and coimmunoprecipitation in vivo suggests the proteins are direct partners in Pc-G mediated repression and this relationship has been evolutionarily conserved.

      The gene products of esc and E(z) bind directly to each other and co-localize at multiple chromosomal sites.

      E(z) protein is ubiquitously distributed in embryonic and larval nuclei and binds many of the same polytene chromosome nuclei as other Pc-G proteins. Lack of E(z) protein activity disrupts chromosome binding by trx protein.

      Although E(z) has been classified as a member of the Polycomb group of genes, it can also be classified as a member of the trithorax group. The requirement for E(z) activity as either a trithorax group or Polycomb group gene depends on the homeotic selector gene locus as well as on spatial and temporal cues.

      In an effort to subdivide the Pc-group genes functionally, the phenotypes of adult flies heterozygous for every pairwise combination of Pc-group mutation were examined. Genetic interactions have been demonstrated between esc, Asx, E(Pc), Pcl, E(z) and sxc. Most duplications of Pc-group genes neither exhibit anterior transformations nor suppress the extra sex comb phenotype of Pc-group mutations, suggesting that not all Pc-group genes behave as predicted by the mass action model. Duplications of E(z) enhance homeotic phenotypes of esc mutants.

      Sections of the Scr regulatory region may be important for regulation of Scr by Polycomb- and trithorax-group genes.

      E(z) activity is required for expression in the imaginal discs of Antp, Ubx, Scr and en. E(z) mutations exhibit interallelic non-complementation with ash1 mutations.

      E(z) mutations can express phenotypes characteristic of mutations in the trx-group of genes. Loss of function for E(z) during early development results in homeotic gene expression defects reminiscent of a trx-group mutation, while loss later in development results in gene expression defects characteristic of a Pc-group mutation.

      The effect of mutations in the E(z) locus on mutagenesis in the y2ns scme double superunstable system has been analysed.

      The intensity of trx binding to larval salivary gland polytene chromosomes is strongly decreased in larvae carrying mutations in E(z).

      A screen for suppressors of nos mutations identified alleles of E(z). E(z) is a negative transcriptional regulator of kni and gt and is required to maintain their expression domain initiated by the maternal hb gradient. A small region of the kni promoter mediates regulation by E(z) and hb. Imprinting at the chromatin level may underlie the determination of anteroposterior polarity in the early embryo.

      Molecular analysis of the E(z) gene.

      The association of the Psc and Su(z)2 proteins with the chromosomes is dependent on the presence of active E(z) protein.

      The bithorax complex genes are regulated by the Pc group of genes, acting via 'Pc group response elements' (PREs), that can work even when removed from the normal bithorax complex context. The Pc group products apparently provide stable memory or imprinting of boundaries which are specified by gap and pair-rule regulators.

      Embryos mutant for two or more Pc group genes (Pc, Scm, Pcl, Psc, Asx, E(Pc), E(z), ph-d, pho and esc) show strong ectopic en expression, but only weak derepression occurs if embryo is mutant at only one of the Pc group genes. This effect is independent of the function of en itself, and wg.

      Mutations of genes in the polycomb group (esc, E(z), Pc, ph-p, ph-d, Scm, Pcl, Sce, Asx, Psc, pho and Antp) cause abnormal segmental development due to the ectopic expression of abd-A and Abd-B. Embryos lacking both maternal and zygotic E(z) product were generated to determine abd-A and Abd-B expression patterns.

      Reduction of E(z)+ activity suppresses the z1 eye colour. Maternally and zygotically produced E(z)+ activity is required to correctly regulate the segment identity genes during embryonic and imaginal development.

      E(z) locus is involved in the suppression of the z1 eye colour and is also associated with homeotic transformations.

      Locus named after original gain-of-function allele E(z)1 (Kalisch and Rasmuson, 1974); subsequently designated polycombeotic (pco) (by Phillips and Shearn, 1980) based on phenotype of lethal homozygotes. Loss of function alleles recovered as (a) recessive lethal mutations (b) reversions of E(z)1 and (c) reversions of the antimorphic allele, E(z)59. Reduction of E(z)+ activity leads to suppression of the z eye color, whereas gain-of-function alleles are dominant enhancers of zeste eye color <up>i.e., z w+/Y; E(z)1/+ males have brownish eyes as do z w+/z+ w+; E(z)1/+ females</up>. E(z)59 an antimorphic allele, is a dominant suppressor of z <up>i.e. z w+; E(z)59/+ females have orange eyes</up>. Hemizygosity for E(z)+ produces a very mild suppression of the z eye color. No effects on eye color in z+ or za backgrounds and effects on eye color not specific to a particular w allele. Reduction of E(z)+ activity also allows ectopic expression of the segment identity genes of the Antennapedia and bithorax gene complexes, resulting in homeotic transformations. This latter effect defines E(z) as a Polycomb-group locus. E(z)61 displays temperature-sensitive suppression of z eye color and homeotic phenotypes. At 22oC, z wis/Y; Hemizygous E(z)61 males have orange eyes and no homeotic transformations. At 29oC, such males have wild-type red eyes and die as pharate adults with strong homeotic transformations of the mesothoracic and metathoracic legs toward the prothoracic state. Embryos produced by E(z)61 homozygous females at 29oC die with homeotic transformations of most segments toward the eighth abdominal segment. Even two copies of paternally contributed E(z)+ does not rescue viability of these embryos. Complete lack of zygotically produced E(z)+ results in early pupal lethality and small imaginal discs. Larval brain squashes from individuals homozygous for an amorphic allele reveal a very low mitotic index; metaphase chromosomes irregularly condensed and fragmented (Gatti and Baker, 1989).

      Relationship to Other Genes
      Source for database merge of

      Source for merge of: l(3)ds12 l(3)SG17

      Additional comments
      Nomenclature History
      Source for database identify of

      Source for identity of: E(z) CG6502

      Nomenclature comments
      Etymology
      Synonyms and Secondary IDs (27)
      Reported As
      Symbol Synonym
      E(z)
      (Bonnet et al., 2026, Fitz-James et al., 2025, Fitz-James et al., 2025, Kyrchanova et al., 2025, Li et al., 2025, Martinez, 2025, Bamgbose and Tulin, 2024, Brown et al., 2024, Gilbert et al., 2024, Lv et al., 2024, Seif and Francis, 2024, Veneti et al., 2024, Wen et al., 2024, Bharti et al., 2023, Brown et al., 2023, Cabrita and Martinho, 2023, Erokhin et al., 2023, Godneeva et al., 2023, Jangam et al., 2023, Lundkvist et al., 2023, McPherson et al., 2023, Pang et al., 2023, Rajan et al., 2023, Yang et al., 2023, Bernués et al., 2022, Bi et al., 2022, Feijão et al., 2022, Fischer et al., 2022, Gaultier et al., 2022, Kang et al., 2022, Richards et al., 2022, Shaposhnikov et al., 2022, Torres-Campana et al., 2022, Akkouche et al., 2021, Bilder et al., 2021, Chaouch and Lasko, 2021, Chaouch et al., 2021, Chetverina et al., 2021, Erokhin et al., 2021, Ghotbi et al., 2021, Hagen et al., 2021, Lindehell et al., 2021, Lucas et al., 2021, Moutaoufik and Tanguay, 2021, Pang et al., 2021, Ponrathnam et al., 2021, Soni et al., 2021, Vidaurre and Chen, 2021, Ward and Moehring, 2021, Barbour et al., 2020, Chetverina et al., 2020, DeLuca et al., 2020, Ghotbi et al., 2020, Gozalo et al., 2020, Gulati et al., 2020, Kuroda et al., 2020, Liu et al., 2020, Loubiere et al., 2020, Meyer-Nava et al., 2020, Morgan and Shilatifard, 2020, Parkhitko et al., 2020, Vissers et al., 2020, Berlandi et al., 2019, Blice-Baum et al., 2019, Bonnet et al., 2019, Cheutin and Cavalli, 2019, Jiang et al., 2019, Leatham-Jensen et al., 2019, Luhur et al., 2019, Moskalev et al., 2019, Parey and Crombach, 2019, Sang Cho et al., 2019, Sneppen and Ringrose, 2019, Umer et al., 2019, Alhaj Abed et al., 2018, Cho et al., 2018, Dasari et al., 2018, Davis and Rebay, 2018, Kennerdell et al., 2018, Lv et al., 2018, Ma et al., 2018, Nishioka et al., 2018, Ogiyama et al., 2018, Rojas-Ríos and Simonelig, 2018, Sadasivam and Huang, 2018, Song et al., 2018, Zhu et al., 2018, Coleman and Struhl, 2017, Feng et al., 2017, Janssens et al., 2017, Kang et al., 2017, Li et al., 2017, Lomaev et al., 2017, Sharma et al., 2017, Transgenic RNAi Project members, 2017-, Zenk et al., 2017, Zhang et al., 2017, Zouaz et al., 2017, Du et al., 2016, Goto et al., 2016, Kahn et al., 2016, Li et al., 2016, Lv et al., 2016, Morimoto et al., 2016, Peng et al., 2016, Piunti and Shilatifard, 2016, Shih et al., 2016, Xia et al., 2016, Zhang et al., 2016, Cesarini et al., 2015, Dequéant et al., 2015, Dietz et al., 2015, Ghasemi et al., 2015, Kang et al., 2015, Lee et al., 2015, McKay et al., 2015, model organism Encyclopedia of Regulatory Network (modERN) Project, 2015-, Singh and Mishra, 2015, Yung et al., 2015, Comoglio and Paro, 2014, Gambetta and Müller, 2014, Gonzalez et al., 2014, Herz et al., 2014, Kim et al., 2014, McElroy et al., 2014, Ost et al., 2014, Rhee et al., 2014, Slattery et al., 2014, Stern et al., 2014, Yan et al., 2014, Aloia et al., 2013, Bengani et al., 2013, Collins and Moon, 2013, Debruhl et al., 2013, Di Croce and Helin, 2013, Iovino et al., 2013, Kwon et al., 2013, Lo Sardo et al., 2013, Mason-Suares et al., 2013, Mulero et al., 2013, Pengelly et al., 2013, Rai et al., 2013, Smith et al., 2013, Vasanthi et al., 2013, Cuddapah et al., 2012, Feller et al., 2012, Hainaut et al., 2012, Herz et al., 2012, Lanzuolo and Orlando, 2012, Matzat et al., 2012, McEachern, 2012, Petruk et al., 2012, Popkova et al., 2012, Sakoparnig et al., 2012, Stepanik and Harte, 2012, Stern et al., 2012, Takács et al., 2012, Yuan et al., 2012, Zhai et al., 2012, Anderson et al., 2011, Cavalli, 2011, Chen et al., 2011, Islam et al., 2011, Katsuyama and Paro, 2011, Kirilly et al., 2011, Nowak et al., 2011, Pruteanu-Malinici et al., 2011, Rodriguez-Jato et al., 2011, Toku et al., 2011, Gandille et al., 2010, Gan et al., 2010, Gan et al., 2010, Herz et al., 2010, Lee et al., 2010, Saj et al., 2010, Siebold et al., 2010, Wilkinson et al., 2010, Chen and Rasmuson-Lestander, 2009, Classen et al., 2009, Gambetta et al., 2009, Gambetta et al., 2009, Khan et al., 2009, Phalke et al., 2009, Tie et al., 2009, Chen et al., 2008, Chen et al., 2008, Fanti et al., 2008, Fujioka et al., 2008, Joshi et al., 2008, Matyunina et al., 2008, Savla et al., 2008, Zhang et al., 2008, Bello et al., 2007, de Ayala Alonso et al., 2007, Goodliffe et al., 2007, Mishra et al., 2007, Nekrasov et al., 2007, Parrish et al., 2007, Ringrose and Paro, 2007, Schuettengruber et al., 2007, Simmons et al., 2007, Klymenko et al., 2006, Maeda and Karch, 2006, Muller and Kassis, 2006, Papp and Muller, 2006, Parrish et al., 2006, Talbert and Henikoff, 2006, Wang et al., 2006, Andreyeva et al., 2005, Brown et al., 2005, Dillon et al., 2005, Kalmykova et al., 2005, Ketel et al., 2005, Lam et al., 2005, Nekrasov et al., 2005, Ali and Bender, 2004, Breiling et al., 2004, Marin, 2003, Huang et al., 2002, Joanis and Lloyd, 2002, Wicker-Thomas and Jallon, 2000)
      l(3)B12
      l(3)SG17
      l(3)ds12
      pco/E(z)
      Secondary FlyBase IDs
      • FBgn0004710
      Datasets (2)
      Study focus (2)
      Experimental Role
      Project
      Project Type
      Title
      • transgene_used
      Protein profiling reveals five principal chromatin types in Drosophila cells.
      • bait_protein
      Genome-wide localization of chromosomal proteins in cell lines by ChIP-chip and ChIP-Seq.
      Study result (0)
      Result
      Result Type
      Title
      External Crossreferences and Linkouts ( 61 )
      Sequence Crossreferences
      NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
      GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
      GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
      RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
      UniProt/GCRP - The gene-centric reference proteome (GCRP) provides a 1:1 mapping between genes and UniProt accessions in which a single 'canonical' isoform represents the product(s) of each protein-coding gene.
      UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
      UniProt/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information
      Other crossreferences
      AlphaFold DB - AlphaFold provides open access to protein structure predictions for the human proteome and other key proteins of interest, to accelerate scientific research.
      BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
      DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
      EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
      FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
      FlyMine - An integrated database for Drosophila genomics
      KEGG Genes - Molecular building blocks of life in the genomic space.
      MARRVEL_MODEL - MARRVEL (model organism gene)
      Linkouts
      BioGRID - A database of protein and genetic interactions.
      Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
      DroID - A comprehensive database of gene and protein interactions.
      DRSC - Results frm RNAi screens
      Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
      FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
      FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
      Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
      Flygut - An atlas of the Drosophila adult midgut
      FlyMet - A comprehensive tissue-specific metabolomics resource for Drosophila.
      iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
      Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
      KEGG Metabolic Pathways - A collection of manually drawn metabolic pathway maps representing knowledge of molecular interaction, reaction and relation networks.
      KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
      MIST (genetic) - An integrated Molecular Interaction Database
      MIST (protein-protein) - An integrated Molecular Interaction Database
      SignaLink - A signaling pathway resource with multi-layered regulatory networks.
      References (598)