Institute of Reproductive and Developmental Biology, Imperial College School of Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Development. 2010 Aug 1;137(15):2483-92. doi: 10.1242/dev.048363. Epub 2010 Jun 23.
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.
多能细胞在囊胚的内细胞团中发育，这是一个由胚胎外层即滋养外胚层包围的细胞嵌合体。我们发现，一组体细胞谱系调节因子（包括 Hox、Gata 和 Sox 因子）携带富含 H3K27me3 和 H3K4me2 的二价染色质，在胚胎外胚层与胚胎（多能）谱系中，通过 Suv39h1 介导的 H3K9me3 和新合成的 DNA 甲基化而被选择性靶向，这在囊胚衍生的干细胞和体内均得到了评估。这种稳定的抑制状态与基因启动子的缺失有关，即在滋养层谱系分化后，通过排除 PRC1（Ring1B）和 RNA 聚合酶 II 复合物，使二价、谱系不当基因上的转录失去预备。总的来说，我们的结果表明，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，并提出了一种在早期发育过程中加强谱系特化的新机制。
