Tao Yu, Zheng Weisheng, Jiang Yonghua, Ding Guitao, Hou Xinfeng, Tang Yitao, Li Yueying, Gao Shuai, Chang Gang, Zhang Xiaobai, Liu Wenqiang, Kou Xiaochen, Wang Hong, Jiang Cizhong, Gao Shaorong
College of Life Science, Beijing Normal University, Beijing, 100875, China.
National Institute of Biological Sciences, NIBS, Beijing, 102206, China.
BMC Biol. 2014 Dec 21;12:109. doi: 10.1186/s12915-014-0109-x.
Nucleosome organization determines the chromatin state, which in turn controls gene expression or silencing. Nucleosome remodeling occurs during somatic cell reprogramming, but it is still unclear to what degree the re-established nucleosome organization of induced pluripotent stem cells (iPSCs) resembles embryonic stem cells (ESCs), and whether the iPSCs inherit some residual gene expression from the parental fibroblast cells.
We generated genome-wide nucleosome maps in mouse ESCs and in iPSCs reprogrammed from somatic cells belonging to three different germ layers using a secondary reprogramming system. Pairwise comparisons showed that the nucleosome organizations in the iPSCs, regardless of the iPSCs' tissue of origin, were nearly identical to the ESCs, but distinct from mouse embryonic fibroblasts (MEF). There is a canonical nucleosome arrangement of -1, nucleosome depletion region, +1, +2, +3, and so on nucleosomes around the transcription start sites of active genes whereas only a nucleosome occupies silent transcriptional units. Transcription factor binding sites possessed characteristic nucleosomal architecture, such that their access was governed by the rotational and translational settings of the nucleosome. Interestingly, the tissue-specific genes were highly expressed only in the parental somatic cells of the corresponding iPS cell line before reprogramming, but had a similar expression level in all the resultant iPSCs and ESCs.
The re-established nucleosome landscape during nuclear reprogramming provides a conserved setting for accessibility of DNA sequences in mouse pluripotent stem cells. No persistent residual expression program or nucleosome positioning of the parental somatic cells that reflected their tissue of origin was passed on to the resulting mouse iPSCs.
核小体组织决定染色质状态，进而控制基因表达或沉默。核小体重塑发生在体细胞重编程过程中，但诱导多能干细胞（iPSC）重新建立的核小体组织在多大程度上类似于胚胎干细胞（ESC），以及iPSC是否从亲本成纤维细胞继承了一些残留的基因表达仍不清楚。
我们使用二次重编程系统在小鼠ESC和从属于三个不同胚层的体细胞重编程而来的iPSC中生成了全基因组核小体图谱。成对比较表明，无论iPSC的起源组织如何，其核小体组织与ESC几乎相同，但与小鼠胚胎成纤维细胞（MEF）不同。在活跃基因的转录起始位点周围存在-1、核小体缺失区域、+1、+2、+3等核小体的典型核小体排列，而只有一个核小体占据沉默转录单元。转录因子结合位点具有特征性的核小体结构，其可及性受核小体的旋转和平移设置控制。有趣的是，组织特异性基因仅在重编程前相应iPSC系的亲本体细胞中高表达，但在所有产生的iPSC和ESC中具有相似的表达水平。
核重编程过程中重新建立的核小体景观为小鼠多能干细胞中DNA序列的可及性提供了保守的环境。亲本体细胞的任何持续残留表达程序或反映其起源组织的核小体定位都没有传递给产生的小鼠iPSC。
