Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
Genes Dev. 2010 Feb 1;24(3):265-76. doi: 10.1101/gad.544410.
Polycomb complexes establish chromatin modifications for maintaining gene repression and are essential for embryonic development in mice. Here we use pluripotent embryonic stem (ES) cells to demonstrate an unexpected redundancy between Polycomb-repressive complex 1 (PRC1) and PRC2 during the formation of differentiated cells. ES cells lacking the function of either PRC1 or PRC2 can differentiate into cells of the three germ layers, whereas simultaneous loss of PRC1 and PRC2 abrogates differentiation. On the molecular level, the differentiation defect is caused by the derepression of a set of genes that is redundantly repressed by PRC1 and PRC2 in ES cells. Furthermore, we find that genomic repeats are Polycomb targets and show that, in the absence of Polycomb complexes, endogenous murine leukemia virus elements can mobilize. This indicates a contribution of the Polycomb group system to the defense against parasitic DNA, and a potential role of genomic repeats in Polycomb-mediated gene regulation.
多梳复合物为维持基因抑制建立染色质修饰，并且对于小鼠胚胎发育至关重要。在这里，我们利用多能胚胎干细胞（ES 细胞）证明了在分化细胞形成过程中，多梳抑制复合物 1（PRC1）和 PRC2 之间存在出乎意料的冗余性。缺乏 PRC1 或 PRC2 功能的 ES 细胞可以分化为三个胚层的细胞，而同时缺失 PRC1 和 PRC2 则会阻断分化。在分子水平上，分化缺陷是由一组基因的去抑制引起的，这些基因在 ES 细胞中被 PRC1 和 PRC2 冗余抑制。此外，我们发现基因组重复序列是多梳复合物的靶点，并表明在缺乏多梳复合物的情况下，内源性鼠白血病病毒元件可以被激活。这表明多梳复合物系统有助于防御寄生 DNA，并且基因组重复序列在多梳复合物介导的基因调控中可能发挥作用。
