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哺乳动物中多梳蛋白介导的Hox基因抑制作用需要必需的剪接体蛋白Sf3b1。

Mammalian polycomb-mediated repression of Hox genes requires the essential spliceosomal protein Sf3b1.

作者信息

Isono Kyoichi, Mizutani-Koseki Yoko, Komori Toshihisa, Schmidt-Zachmann Marion S, Koseki Haruhiko

机构信息

Developmental Genetics Group, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama 230-0045, Japan.

出版信息

Genes Dev. 2005 Mar 1;19(5):536-41. doi: 10.1101/gad.1284605.

Abstract

Polycomb group (PcG) proteins are responsible for the stable repression of homeotic (Hox) genes by forming multimeric protein complexes. We show (1) physical interaction between components of the U2 small nuclear ribonucleoprotein particle (U2 snRNP), including Sf3b1 and PcG proteins Zfp144 and Rnf2; and (2) that Sf3b1 heterozygous mice exhibit skeletal transformations concomitant with ectopic Hox expressions. These alterations are enhanced by Zfp144 mutation but repressed by Mll mutation (a trithorax-group gene). Importantly, the levels of Sf3b1 in PcG complexes were decreased in Sf3b1-heterozygous embryos. These findings suggest that Sf3b1-PcG protein interaction is essential for true PcG-mediated repression of Hox genes.

摘要

多梳蛋白家族(PcG)通过形成多聚体蛋白复合物来稳定抑制同源异型(Hox)基因。我们发现:(1)U2小核核糖核蛋白颗粒(U2 snRNP)的组分之间存在物理相互作用,包括Sf3b1以及PcG蛋白Zfp144和Rnf2;(2)Sf3b1杂合小鼠表现出骨骼变形并伴有异位Hox表达。这些改变在Zfp144突变时增强,但在Mll突变(一个三胸蛋白家族基因)时受到抑制。重要的是,在Sf3b1杂合胚胎中,PcG复合物中Sf3b1的水平降低。这些发现表明,Sf3b1-PcG蛋白相互作用对于PcG介导的Hox基因真正抑制至关重要。

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