A Vertebrate Polycomb Response Element Governs Segmentation of the Posterior Hindbrain
A Vertebrate Polycomb Response Element Governs Segmentation of the Posterior Hindbrain
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DOI：
10.1016/j.cell.2009.08.020
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发表时间：
2009-09-04
期刊：
影响因子：
64.5
通讯作者：
Cordes, Sabine P.
中科院分区：
文献类型：
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作者：
Sing, Angela;Pannell, Dylan;Cordes, Sabine P.
多梳蛋白(PcG)和三胸蛋白(TrxG)的染色质重塑调节所有后生动物的基因表达。两个主要的复合体，多梳抑制复合体1和2(PRC1和PRC2)，被认为在果蝇和哺乳动物中介导PcG依赖的抑制。在果蝇中，PcG/trxG蛋白复合体被PcG/trxG反应元件(Pres)招募。然而，目前还不清楚PcG/trxG在脊椎动物中是如何恢复的。在这里，我们已经确定了脊椎动物的Pre，Pre-KR，它调节小鼠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PcG/trxG依赖的方式抑制基因表达。PRC1和2与最小的Pre-KR区域结合，当异位引入时，可以招募稳定的PRC1结合，但只有微弱的PRC2结合，这表明PRC1和2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是脊椎动物PcG/trxG染色质重塑的进入位点。
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 recuited 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.