Elsevier

Genomics

Volume 37, Issue 2, 15 October 1996, Pages 161-171
Genomics

Regular Article
Characterization ofEZH1,a Human Homolog ofDrosophila Enhancer of zestenearBRCA1

https://doi.org/10.1006/geno.1996.0537Get rights and content
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Abstract

Recent transcription mapping efforts within chromosome 17q21 have led to the identification of a human homolog of theDrosophilageneEnhancer 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 humanEZH1(Enhancer of zeste homolog 1) and compare the respective protein sequences in both species.EZH1encodes a protein of 747 amino acids that displays 55% amino acid identity overall (70% similarity) withDrosophila E(z). The strongest homology was noted (79% identity, 89% similarity) within the carboxy-terminal 245 amino acids, including the SET domain, a region ofE(z) also conserved in otherDrosophilaproteins with roles in development and/or chromatin structure. A large Cys-rich region with a novel spatial pattern of cysteine residues was also conserved in bothEZH1andE(z). The strong sequence conservation suggests potential roles forEZH1in human development as a transcriptional regulator and as a component of protein complexes that stably maintain heterochromatin.EZH1is 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 involvingEZH1and a tandemly linked geneGPR2and suggests a potential mechanism for modifying theEZH1protein in the conserved C-terminal domain. The sequence and isolated cDNAs will provide useful reagents for determining the function ofEZH1and the importance of the evolutionarily conserved domains.

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