Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31
Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31
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DOI：
10.1093/emboj/18.7.1923
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发表时间：
1999-04-01
期刊：
影响因子：
11.4
通讯作者：
Jenuwein, T
中科院分区：
文献类型：
--
作者：
Aagaard, L;Laible, G;Jenuwein, T
Chrome和SET结构域是存在于染色体蛋白中的保守序列，其在基因表达的表观遗传控制中起作用，推测是通过调节高阶染色质。基于来自SET结构域的序列信息，我们分离了位置效应杂色（PEV）Su（var）3-9的显性果蝇修饰剂的人（SUV 39 H1）和小鼠（Suv 39 h1）同源物。除了SET结构域之外，哺乳动物同源物还含有特征性的Chrome结构域，这是一种也在粟酒裂殖酵母沉默因子clr 4中保留的组合。人SUV 39 H1增加转基因苍蝇中近着丝粒白色标记基因抑制的潜力证明了染色质依赖性基因调节。对多种哺乳动物细胞系中的内源性Suv 39 h1/SUV 39 H1蛋白的免疫检测揭示了在间期期间在异染色质灶处的富集分布和在中期期间的着丝粒特异性定位。此外，Suv 39 h1/SUV 39 H1蛋白与M31相关，M31是目前唯一的其他特征性哺乳动物SU（VAR）同源物，这些数据表明哺乳动物SU（VAR）复合物的存在，并将Suv 39 h1/SUV 39 H1定义为哺乳动物高阶染色质的新组分。
The chrome and SET domains are conserved sequence moths present in chromosomal proteins that function in epigenetic control of gene expression, presumably by modulating higher order chromatin, Based on sequence information from the SET domain, we have isolated human (SUV39H1) and mouse (Suv39h1) homologues of the dominant Drosophila modifier of position-effect-variegation (PEV) Su(var)3-9. Mammalian homologues contain, in addition to the SET domain, the characteristic chrome domain, a combination that is also preserved in the Schizosaccharyomyces pombe silencing factor clr4. Chromatin-dependent gene regulation is demonstrated by the potential of human SUV39H1 to increase repression of the pericentromeric white marker gene in transgenic flies. Immunodetection of endogenous Suv39h1/SUV39H1 proteins in a variety of mammalian cell lines reveals enriched distribution at heterochromatic foci during interphase and centromere-specific localization during metaphase, In addition, Suv39h1/SUV39H1 proteins associate with M31, currently the only other characterized mammalian SU(VAR) homologue, These data indicate the existence of a mammalian SU(VAR) complex and define Suv39h1/SUV39H1 as novel components of mammalian higher order chromatin.