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脊椎动物的多梳反应元件调控后脑后部的分段。

A vertebrate Polycomb response element governs segmentation of the posterior hindbrain.

作者信息

Sing Angela, Pannell Dylan, Karaiskakis Angelo, Sturgeon Kendra, Djabali Malek, Ellis James, Lipshitz Howard D, Cordes Sabine P

机构信息

Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, ON, M5G 1X5, Canada.

出版信息

Cell. 2009 Sep 4;138(5):885-97. doi: 10.1016/j.cell.2009.08.020.

Abstract

Chromatin remodeling by Polycomb group (PcG) and trithorax group (trxG) proteins regulates gene expression in all metazoans. Two major complexes, Polycomb repressive complexes 1 and 2 (PRC1 and PRC2), are thought to mediate PcG-dependent repression in flies and mammals. In Drosophila, PcG/trxG protein complexes are recruited by PcG/trxG response elements (PREs). However, it has been unclear how PcG/trxG are recruited in vertebrates. Here we have identified a vertebrate PRE, PRE-kr, that regulates expression of the mouse MafB/Kreisler gene. PRE-kr recruits PcG proteins in flies and mouse F9 cells and represses gene expression in a PcG/trxG-dependent manner. PRC1 and 2 bind to a minimal PRE-kr region, which can recruit stable PRC1 binding but only weak PRC2 binding when introduced ectopically, suggesting that PRC1 and 2 have different binding requirements. Thus, we provide evidence that similar to invertebrates, PREs act as entry sites for PcG/trxG chromatin remodeling in vertebrates.

摘要

多梳蛋白家族(PcG)和三胸蛋白家族(trxG)蛋白介导的染色质重塑调控着所有后生动物的基因表达。人们认为,两个主要的复合物,即多梳抑制复合物1和2(PRC1和PRC2),在果蝇和哺乳动物中介导依赖于PcG的基因抑制作用。在果蝇中,PcG/trxG蛋白复合物由PcG/trxG反应元件(PREs)招募。然而,PcG/trxG在脊椎动物中是如何被招募的尚不清楚。在此,我们鉴定出了一种脊椎动物PRE,即PRE-kr,它调控小鼠MafB/Kreisler基因的表达。PRE-kr在果蝇和小鼠F9细胞中招募PcG蛋白,并以依赖于PcG/trxG的方式抑制基因表达。PRC1和PRC2结合到一个最小的PRE-kr区域,当异位导入时,该区域可招募稳定的PRC1结合,但只能招募较弱的PRC2结合,这表明PRC1和PRC2具有不同的结合要求。因此,我们提供的证据表明,与无脊椎动物类似,PREs在脊椎动物中作为PcG/trxG染色质重塑的起始位点。

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