Constitutive heterochromatin reorganization during somatic cell reprogramming
Constitutive heterochromatin reorganization during somatic cell reprogramming
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DOI：
10.1038/emboj.2011.96
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发表时间：
2011-05-04
期刊：
影响因子：
11.4
通讯作者：
Bazett-Jones, David P.
中科院分区：
文献类型：
--
作者：
Fussner, Eden;Djuric, Ugljesa;Bazett-Jones, David P.
诱导多能干细胞重编程是一个渐进的表观遗传过程，通过清除和建立抑制性表观遗传标记来重新激活多能转录网络。与基因座特异性表观遗传变化相反，异染色质结构域在重编程过程中经历表观遗传重置，但对异染色质超微结构的影响尚不清楚。在这里，我们的特点的物理结构的异染色质结构域在全部和部分小鼠iPS细胞的相关电子光谱成像。在体细胞和部分iPS细胞中，由H3 K9 me 3标记的组成型异染色质高度区室化为密集染色质纤维的染色质中心结构。相比之下，在多能胚胎干细胞和完整的iPS细胞中，染色中心边界的定义很差，并且其特征在于在高Nanog表达细胞中异常分散的10 nm异染色质纤维，包括分化前的小鼠囊胚的多能细胞。这种异染色质重组伴随着逆转录病毒沉默，在通过MEK/GSK 3 2 i抑制剂处理转化部分iPS细胞期间。因此，组成型异染色质在部分iPS细胞中被压实，但随着获得完全重编程的iPS细胞状态而重组成分散的10 nm染色质纤维。The EMBO Journal（2011）30，1778-1789. doi：10.1038/daj.2011.96; 2011年4月5日在线发布
Induced pluripotent stem (iPS) cell reprogramming is a gradual epigenetic process that reactivates the pluripotent transcriptional network by erasing and establishing repressive epigenetic marks. In contrast to loci-specific epigenetic changes, heterochromatin domains undergo epigenetic resetting during the reprogramming process, but the effect on the heterochromatin ultrastructure is not known. Here, we characterize the physical structure of heterochromatin domains in full and partial mouse iPS cells by correlative electron spectroscopic imaging. In somatic and partial iPS cells, constitutive heterochromatin marked by H3K9me3 is highly compartmentalized into chromocentre structures of densely packed chromatin fibres. In contrast, chromocentre boundaries are poorly defined in pluripotent embryonic stem and full iPS cells, and are characterized by unusually dispersed 10nm heterochromatin fibres in high Nanog-expressing cells, including pluripotent cells of the mouse blastocyst before differentiation. This heterochromatin reorganization accompanies retroviral silencing during conversion of partial iPS cells by MEK/GSK3 2i inhibitor treatment. Thus, constitutive heterochromatin is compacted in partial iPS cells but reorganizes into dispersed 10nm chromatin fibres as the fully reprogrammed iPS cell state is acquired. The EMBO Journal (2011) 30, 1778-1789. doi:10.1038/emboj.2011.96; Published online 5 April 2011