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首页> 外文期刊>Epigenetics & Chromatin >Maintenance of active chromatin states by HMGN2 is required for stem cell identity in a pluripotent stem cell model
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Maintenance of active chromatin states by HMGN2 is required for stem cell identity in a pluripotent stem cell model

机译：HMGN2在多能干细胞模型中需要HMGN2的活性染色质状态的维持

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Members of the HMGN protein family modulate chromatin structure and influence epigenetic modifications. HMGN1 and HMGN2 are highly expressed during early development and in the neural stem/progenitor cells of the developing and adult brain. Here, we investigate whether HMGN proteins contribute to the chromatin plasticity and epigenetic regulation that is essential for maintaining pluripotency in stem cells. We show that loss of Hmgn1 or Hmgn2 in pluripotent embryonal carcinoma cells leads to increased levels of spontaneous neuronal differentiation. This is accompanied by the loss of pluripotency markers Nanog and Ssea1, and increased expression of the pro-neural transcription factors Neurog1 and Ascl1. Neural stem cells derived from these Hmgn-knockout lines also show increased spontaneous neuronal differentiation and Neurog1 expression. The loss of HMGN2 leads to a global reduction in H3K9 acetylation, and disrupts the profile of H3K4me3, H3K9ac, H3K27ac and H3K122ac at the Nanog and Oct4 loci. At endodermal/mesodermal genes, Hmgn2-knockout cells show a switch from a bivalent to a repressive chromatin configuration. However, at neuronal lineage genes whose expression is increased, no epigenetic changes are observed and their bivalent states are retained following the loss of HMGN2. We conclude that HMGN1 and HMGN2 maintain the identity of pluripotent embryonal carcinoma cells by optimising the pluripotency transcription factor network and protecting the cells from precocious differentiation. Our evidence suggests that HMGN2 regulates active and bivalent genes by promoting an epigenetic landscape of active histone modifications at promoters and enhancers.
机译：HMGN蛋白质系列的成员调节染色质结构并影响表观遗传修饰。 HMGN1和HMGN2在早期发育和显影和成人脑的神经茎/祖细胞中高度表达。在这里，我们研究了HMGN蛋白是否有助于染色质塑性和表观遗传调节，这对于维持干细胞中的多能性是必不可少的。我们表明，多能胚胎癌细胞中HMGN1或HMGN2的丧失导致自发神经元分化的水平增加。这伴随着多能标志物纳米和SSEA1的丧失，并增加了亲神经转录因子Neurog1和AsCl1的表达。源自这些HMGN敲除线的神经干细胞也显示出增加的自发神经元分化和神经痛1表达。 HMGN2的丧失导致全球H3K9乙酰化的降低，并在纳米和Oct4基因座上破坏H3K4ME3，H3K9AC，H3K27AC和H3K122Ac的轮廓。在内胚层/中胚层基因中，HMGN2敲除细胞显示出从二价的开关到抑制染色质构型构型。然而，在表达增加的神经元谱系基因下，未观察到表观遗传变化，并且在损失HMGN2后保留它们的二价状态。我们得出结论，HMGN1和HMGN2通过优化多能转录因子网络并保护细胞免受预焦分化来维持多能胚胎癌细胞的身份。我们的证据表明，HMGN2通过在启动子和增强剂促进活性组蛋白修饰的表观遗传景观来调节活性和二价基因。

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