title: Characterization of EZH1, a human homolog of Drosophila Enhancer of zeste near BRCA1.
abstract: Recent transcription mapping efforts within chromosome 17q21 have led to the identification of a human homolog of the Drosophila gene Enhancer of zeste, E(z). A member of the Polycomb group (Pc-G) of proteins, Drosophila E(z) acts as a negative regulator of the segment identity genes of the Antennapedia and Bithorax complexes. Here we report the full-length protein coding sequence of human EZH1 (Enhancer of zeste homolog 1) and compare the respective protein sequences in both species. EZH1 encodes a protein of 747 amino acids that displays 55% amino acid identity overall (70% similarity) with Drosophila E(z). The strongest homology was noted (79% identity, 89% similarity) within the carboxy-terminal 245 amino acids, including the SET domain, a region of E(z) also conserved in other Drosophila proteins with roles in development and/or chromatin structure. A large Cysrich region with a novel spatial pattern of cysteine residues was also conserved in both EZH1 and E(z). The strong sequence conservation suggest potential roles for EZH1 in human development as a transcriptional regulator and as a component of protein complexes that stably maintain heterochromatin. EZH1 is expressed as two major transcripts in all adult and fetal human tissues surveyed; comparison of cloned cDNAs suggests that alternative splicing may account for at least part of the transcript size difference. Analysis of one cDNA revealed an unusual splicing event involving EZH1 and a tandemly linked gene GPR2 and suggests a potential mechanism for modifying the EZH1 protein in the conserved C-terminal domain. The sequence and isolated cDNAs will provide useful reagents for determining the function of EZH1 and the importance of the evolutionarily conserved domains.
authors.affiliation: Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor 48109, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Abel
authors.forename: L C
authors.initials: LC
authors.lastname: Brody
authors.forename: J M
authors.initials: JM
authors.lastname: Valdes
authors.forename: M R
authors.initials: MR
authors.lastname: Erdos
authors.forename: D R
authors.initials: DR
authors.lastname: McKinley
authors.forename: L H
authors.initials: LH
authors.lastname: Castilla
authors.forename: S D
authors.initials: SD
authors.lastname: Merajver
authors.forename: F J
authors.initials: FJ
authors.lastname: Couch
authors.forename: L S
authors.initials: LS
authors.lastname: Friedman
authors.forename: E A
authors.initials: EA
authors.lastname: Ostermeyer
authors.forename: E D
authors.initials: ED
authors.lastname: Lynch
authors.forename: M C
authors.initials: MC
authors.lastname: King
authors.forename: P L
authors.initials: PL
authors.lastname: Welcsh
authors.forename: S
authors.initials: S
authors.lastname: Osborne-Lawrence
authors.forename: M
authors.initials: M
authors.lastname: Spillman
authors.forename: A M
authors.initials: AM
authors.lastname: Bowcock
authors.forename: F S
authors.initials: FS
authors.lastname: Collins
authors.forename: B L
authors.initials: BL
authors.lastname: Weber
mesh_terms: D000328:Adult; D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics*; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D004330:Drosophila; D029721:Drosophila Proteins; D015870:Gene Expression; D006801:Humans; D019476:Insect Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D063151:Polycomb Repressive Complex 2; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
chemical_list: D019313:BRCA1 Protein; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C083329:E(z) protein, Drosophila; C103523:EZH1 protein, human; C498408:Ezh1 protein, mouse; D063151:Polycomb Repressive Complex 2