Genome-wide nucleosome positioning during embryonic stem cell development
Genome-wide nucleosome positioning during embryonic stem cell development
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DOI：
10.1038/nsmb.2419
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发表时间：
2012-11-01
影响因子：
16.8
通讯作者：
Rippe, Karsten
中科院分区：
文献类型：
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作者：
Teif, Vladimir B.;Vainshtein, Yevhen;Rippe, Karsten
我们确定了小鼠胚胎干细胞及其神经祖细胞和胚胎成纤维细胞对应物的全基因组核小体占有率，以评估与谱系定型期间核小体定位相关的特征。转录因子对核小体占据率低（Myc、Klf4 和 Zfx）或高（Nanog、Oct4 和 Sox2）位点的细胞类型和蛋白质特异性结合偏好以及 CTCF 的复杂模式都得到了鉴定。转录起始位点和转录终止位点周围的核小体耗尽区域很宽，对于活性基因来说更加明显，根据 CpG 含量或组蛋白甲基化标记分类的启动子具有不同的模式。在整个基因组中，核小体占据与某些组蛋白甲基化或乙酰化修饰相关。此外，平均核小体重复长度在分化过程中增加了 5-7 个碱基对，并且特定区域存在局部变化。我们的结果揭示了涉及核小体重新定位的细胞分化的调节机制。
We determined genome-wide nucleosome occupancies in mouse embryonic stem cells and their neural progenitor and embryonic fibroblast counterparts to assess features associated with nucleosome positioning during lineage commitment. Cell-type-and protein-specific binding preferences of transcription factors to sites with either low (Myc, Klf4 and Zfx) or high (Nanog, Oct4 and Sox2) nucleosome occupancy as well as complex patterns for CTCF were identified. Nucleosome-depleted regions around transcription start and transcription termination sites were broad and more pronounced for active genes, with distinct patterns for promoters classified according to CpG content or histone methylation marks. Throughout the genome, nucleosome occupancy was correlated with certain histone methylation or acetylation modifications. In addition, the average nucleosome repeat length increased during differentiation by 5-7 base pairs, with local variations for specific regions. Our results reveal regulatory mechanisms of cell differentiation that involve nucleosome repositioning.