Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment
Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment
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DOI：
10.1242/dev.048363
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发表时间：
2010-08-01
期刊：
影响因子：
4.6
通讯作者：
Azuara, Veronique
中科院分区：
文献类型：
--
作者：
Alder, Olivia;Lavial, Fabrice;Azuara, Veronique
多能细胞在囊胚的内细胞团中发育，囊胚是被胚外层（滋养外胚层）包围的细胞镶嵌体。我们表明，一组体细胞谱系调节（包括Hox，加塔和Sox因子），携带二价染色质丰富的H3K27 me3和H3K4 me2的选择性靶向Suv39 h1介导的H3K9 me3和从头DNA甲基化在胚胎外与胚胎（多能）谱系，评估在胚泡来源的干细胞和体内。这种稳定的抑制状态与通过排除PRC1（Ring1B）和RNA聚合酶II复合物在滋养层谱系定型时在二价、谱系不适当基因处的基因启动转录的损失有关。总的来说，我们的研究结果表明，Ring1B和Suv39h1在调节关键发育基因的不同染色质状态方面具有相互排斥的作用，并提出了一种新的机制，通过这种机制，可以在早期发育过程中加强谱系特异性。
Pluripotent cells develop within the inner cell mass of blastocysts, a mosaic of cells surrounded by an extra-embryonic layer, the trophectoderm. We show that a set of somatic lineage regulators (including Hox, Gata and Sox factors) that carry bivalent chromatin enriched in H3K27me3 and H3K4me2 are selectively targeted by Suv39h1-mediated H3K9me3 and de novo DNA methylation in extra-embryonic versus embryonic (pluripotent) lineages, as assessed both in blastocyst-derived stem cells and in vivo. This stably repressed state is linked with a loss of gene priming for transcription through the exclusion of PRC1 (Ring1B) and RNA polymerase II complexes at bivalent, lineage-inappropriate genes upon trophoblast lineage commitment. Collectively, our results suggest a mutually exclusive role for Ring1B and Suv39h1 in regulating distinct chromatin states at key developmental genes and propose a novel mechanism by which lineage specification can be reinforced during early development.