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首页> 外文期刊>Epigenetics: official journal of the DNA Methylation Society >Nucleosome positioning changes during human embryonic stem cell differentiation
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Nucleosome positioning changes during human embryonic stem cell differentiation

机译：人类胚胎干细胞分化过程中核小体的定位变化

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摘要

Nucleosomes are the basic unit of chromatin. Nucleosome positioning (NP) plays a key role in transcriptional regulation and other biological processes. To better understand NP we used MNase-seq to investigate changes that occur as human embryonic stem cells (hESCs) transition to nascent mesoderm and then to smooth muscle cells (SMCs). Compared to differentiated cell derivatives, nucleosome occupancy at promoters and other notable genic sites, such as exon/intron junctions and adjacent regions, in hESCs shows a stronger correlation with transcript abundance and is less influenced by sequence content. Upon hESC differentiation, genes being silenced, but not genes being activated, display a substantial change in nucleosome occupancy at their promoters. Genome-wide, we detected a shift of NP to regions of higher G+C content as hESCs differentiate to SMCs. Notably, genomic regions with higher nucleosome occupancy harbor twice as many G <-> C changes but fewer than half A <-> T changes, compared to regions with lower nucleosome occupancy. Finally, our analysis indicates that the hESC genome is not rearranged and has a sequence mutation rate resembling normal human genomes. Our study reveals another unique feature of hESC chromatin, and sheds light on the relationship between nucleosome occupancy and sequence G+C content.
机译：核小体是染色质的基本单位。核小体定位（NP）在转录调控和其他生物学过程中起关键作用。为了更好地理解NP，我们使用MNase-seq研究了人类胚胎干细胞（hESC）过渡到新生中胚层，然后再过渡到平滑肌细胞（SMCs）时发生的变化。与分化的细胞衍生物相比，hESCs在启动子和其他显着基因位点（如外显子/内含子连接处和邻近区域）处的核小体占有率与转录本丰度具有更强的相关性，并且受序列含量的影响较小。在hESC分化后，沉默的基因（而不是激活的基因）在其启动子上显示出核小体占用率的显着变化。在全基因组范围内，由于hESC分化为SMC，我们检测到NP转移到G + C含量更高的区域。值得注意的是，与具有较低核小体占有率的区域相比，具有较高核小体占有率的基因组区域具有两倍的G-C变化但少于一半的A-T变化。最后，我们的分析表明，hESC基因组未重排，其序列突变率与正常人基因组相似。我们的研究揭示了hESC染色质的另一个独特特征，并阐明了核小体占用与序列G + C含量之间的关系。

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