SETD7 Regulates the Differentiation of Human Embryonic Stem Cells.
SETD7 Regulates the Differentiation of Human Embryonic Stem Cells.
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DOI：
10.1371/journal.pone.0149502
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Barrero MJ
中科院分区：
文献类型：
--
作者：
Castaño J;Morera C;Sesé B;Boue S;Bonet-Costa C;Martí M;Roque A;Jordan A;Barrero MJ
在再生医学中成功使用特化细胞需要优化目前使用的分化方案。了解人类多能细胞分化过程中发生的分子事件对于改进这些方案和产生高质量的分化细胞至关重要。在努力了解的分子机制，管理分化，我们确定甲基转移酶SETD7高度诱导人类胚胎干细胞的分化过程中，诱导多能细胞和体细胞之间的差异表达。敲低SETD7可导致人胚胎干细胞的分化缺陷，包括多能性相关基因沉默和分化基因诱导的延迟。我们发现，SETD7甲基化接头组蛋白H1在体外引起H1的构象变化。这些效应与在分化期间在SETD7敲低中H1向多能性基因OCT 4和NANOG的募集减少相关，这可能影响分化期间这些基因的适当沉默。
The successful use of specialized cells in regenerative medicine requires an optimization in the differentiation protocols that are currently used. Understanding the molecular events that take place during the differentiation of human pluripotent cells is essential for the improvement of these protocols and the generation of high quality differentiated cells. In an effort to understand the molecular mechanisms that govern differentiation we identify the methyltransferase SETD7 as highly induced during the differentiation of human embryonic stem cells and differentially expressed between induced pluripotent cells and somatic cells. Knock-down of SETD7 causes differentiation defects in human embryonic stem cell including delay in both the silencing of pluripotency-related genes and the induction of differentiation genes. We show that SETD7 methylates linker histone H1 in vitro causing conformational changes in H1. These effects correlate with a decrease in the recruitment of H1 to the pluripotency genes OCT4 and NANOG during differentiation in the SETD7 knock down that might affect the proper silencing of these genes during differentiation.