Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2) that maps to chromosome 21q22.2

Genomics. 1996 Nov 15;38(1):30-7. doi: 10.1006/geno.1996.0588.

Abstract

To identify genes that map on human chromosome 21 (HC21) and that may contribute to the phenotype of Down syndrome (DS), exon trapping was applied to cosmid DNA from an HC21-specific library LL21NCO2-Q. More than 550 potential exons were cloned and partially characterized. One of these, hmc23b04 (GenBank X88270) showed strong homology to the Drosophila Enhancer of zeste protein (GenBank U00180) from amino acid 665 to 694 (p = 7.6 x 10(-11). We have cloned the full-length cDNA for this human homolog of the Drosophila E(z) gene (termed EZH2) and mapped it to within YACs 64f11 and 809b11 between markers D21S65 and ERG on human chromosome 21q22.2. Sequence analysis indicates that EZH2 encodes a 746-amino-acid polypeptide that shows 60.5% identity to the Drosophila E(z) protein and contains a trithorax-like domain and a DNA-binding motif. Northern blot analysis revealed that EZH2 is expressed in several tissues. Alternatively spliced mRNA species have been observed. The Drosophila E(z) protein is a member of the polycomb group genes that maintain homeotic gene repression and are thought to control gene expression by regulating chromatin. The strong sequence conservation suggests a possible function of EZH2 in regulation of gene transcription and chromatin structure; it may therefore contribute to certain phenotypes of Down syndrome by altered regulation of its target genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Blotting, Southern
  • Chromosome Mapping
  • Chromosomes, Human, Pair 21*
  • Cloning, Molecular
  • Drosophila
  • Drosophila Proteins*
  • Humans
  • Insect Proteins / genetics*
  • Molecular Sequence Data
  • Nuclear Proteins / genetics*
  • Polycomb Repressive Complex 2
  • Polymerase Chain Reaction
  • Repressor Proteins*
  • Sequence Homology, Amino Acid

Substances

  • Drosophila Proteins
  • Insect Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • E(z) protein, Drosophila
  • Polycomb Repressive Complex 2

Associated data

  • GENBANK/H75287
  • GENBANK/T79837
  • GENBANK/T89364
  • GENBANK/T99430
  • GENBANK/T99536
  • GENBANK/U00180
  • GENBANK/X88270
  • GENBANK/X95653
  • GENBANK/Z40549