Abel K J, Brody L C, Valdes J M, Erdos M R, McKinley D R, Castilla L H, Merajver S D, Couch F J, Friedman L S, Ostermeyer E A, Lynch E D, King M C, Welcsh P L, Osborne-Lawrence S, Spillman M, Bowcock A M, Collins F S, Weber B L
Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor 48109, USA.
Genomics. 1996 Oct 15;37(2):161-71. doi: 10.1006/geno.1996.0537.
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.
最近在17号染色体q21区域进行的转录图谱绘制工作，导致了果蝇基因zeste增强子（E(z)）人类同源物的鉴定。果蝇E(z)是多梳蛋白家族（Pc-G）的成员之一，作为触角足复合体和双胸复合体的节段身份基因的负调节因子。在此，我们报告人类EZH1（zeste增强子同源物1）的全长蛋白质编码序列，并比较这两个物种各自的蛋白质序列。EZH1编码一个由747个氨基酸组成的蛋白质，与果蝇E(z)的氨基酸序列总体一致性为55%（相似性为70%）。在羧基末端的245个氨基酸中观察到最强的同源性（一致性为79%，相似性为89%），包括SET结构域，E(z)的这一区域在其他果蝇蛋白质中也保守，这些蛋白质在发育和/或染色质结构中起作用。一个具有新型半胱氨酸残基空间模式的大的富含半胱氨酸区域在EZH1和E(z)中也都保守。强烈的序列保守性表明EZH1在人类发育中作为转录调节因子以及作为稳定维持异染色质的蛋白质复合物的组成部分具有潜在作用。EZH1在所有检测的成人和胎儿人类组织中均以两种主要转录本形式表达；对克隆cDNA的比较表明选择性剪接可能至少部分解释了转录本大小差异。对一个cDNA的分析揭示了一个涉及EZH1和一个串联连接基因GPR2的异常剪接事件，并提示了一种在保守的C末端结构域修饰EZH1蛋白的潜在机制。该序列和分离的cDNA将为确定EZH1的功能以及进化保守结构域的重要性提供有用的试剂。
