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论文题目
YY1 safeguard multidimensional epigenetic landscape associated with extended pluripotency
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作者
Xiaotao Dong,？Rong Guo,？Tianrong Ji,？Jie Zhang,？Jun Xu,？Yaoyi Li,？Yingliang Sheng,？Yuxiang Wang,？Ke Fang,？Yulin Wen,？Bei Liu,？Gongcheng Hu,？Hongkui Deng,？Hongjie Yao
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论文出处
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刊物名称
Nucleic Acids Research
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年卷期页
2022, 50, 21, 12019-12038
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联系作者
Hongjie Yao
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影响因子
19.160
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摘要
Although extended pluripotent stem cells (EPSCs) have the potential to form both embryonic and extraembryonic lineages, how their transcriptional regulatory mechanism differs from that of embryonic stem cells (ESCs) remains unclear. Here, we discovered that YY1 binds to specific open chromatin regions in EPSCs. Yy1 depletion in EPSCs leads to a gene expression pattern more similar to that of ESCs than control EPSCs. Moreover, Yy1 depletion triggers a series of epigenetic crosstalk activities, including changes in DNA methylation, histone modifications and high-order chromatin structures. Yy1 depletion in EPSCs disrupts the enhancer-promoter (EP) interactions of EPSC-specific genes, including Dnmt3l. Yy1 loss results in DNA hypomethylation and dramatically reduces the enrichment of H3K4me3 and H3K27ac on the promoters of EPSC-specific genes by upregulating the expression of Kdm5c and Hdac6 through facilitating the formation of CCCTC-binding factor (CTCF)-mediated EP interactions surrounding their loci. Furthermore, single-cell RNA sequencing (scRNA-seq) experiments revealed that YY1 is required for the derivation of extraembryonic endoderm (XEN)-like cells from EPSCs in vitro. Together, this study reveals that YY1 functions as a key regulator of multidimensional epigenetic crosstalk associated with extended pluripotency.
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英文摘要
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外单位作者单位
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