1. Rbbp4 Suppresses Premature Differentiation of Embryonic Stem Cells
- Author
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Qing Jiang, Congcong Wang, Shuang Liu, Ting Su, Yaru Zhu, Yikai Huang, Yin Xia, Kunying Hao, Jinzhong Qin, and Lixia Dong
- Subjects
0301 basic medicine ,Sox2 ,Oct4 ,macromolecular substances ,Germ layer ,self-renewal ,Methylation ,Biochemistry ,Article ,Cell Line ,Histones ,Gene Knockout Techniques ,Mice ,03 medical and health sciences ,0302 clinical medicine ,SOX2 ,Genetics ,Animals ,Humans ,Gene silencing ,RBBP4 ,Cell Self Renewal ,Psychological repression ,Embryonic Stem Cells ,mesendoderm ,biology ,SOXB1 Transcription Factors ,Polycomb Repressive Complex 2 ,Gene Expression Regulation, Developmental ,Gene targeting ,Cell Differentiation ,Cell Biology ,pluripotency ,PRC2 ,Embryonic stem cell ,Cell biology ,HEK293 Cells ,030104 developmental biology ,embryonic structures ,biology.protein ,Chromatin Immunoprecipitation Sequencing ,Retinoblastoma-Binding Protein 4 ,polycomb ,Octamer Transcription Factor-3 ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Summary Polycomb group (PcG) proteins exist in distinct multi-protein complexes and play a central role in silencing developmental genes, yet the underlying mechanisms remain elusive. Here, we show that deficiency of retinoblastoma binding protein 4 (RBBP4), a component of the Polycomb repressive complex 2 (PRC2), in embryonic stem cells (ESCs) leads to spontaneous differentiation into mesendodermal lineages. We further show that Rbbp4 and core PRC2 share an important number of common genomic targets, encoding regulators involved in early germ layer specification. Moreover, we find that Rbbp4 is absolutely essential for genomic targeting of PRC2 to a subset of developmental genes. Interestingly, we demonstrate that Rbbp4 is necessary for sustaining the expression of Oct4 and Sox2 and that the forced co-expression of Oct4 and Sox2 fully rescues the pluripotency of Rbbp4-null ESCs. Therefore, our study indicates that Rbbp4 links maintenance of the pluripotency regulatory network with repression of mesendoderm lineages., Graphical Abstract, Highlights • RBBP4 deficiency in ESCs leads to spontaneous differentiation into mesendodermal lineages • Rbbp4 binding sites in ESCs substantially overlap with PRC2 binding • Rbbp4 is absolutely essential for PRC2 chromatin occupancy • Rbbp4 is necessary for sustaining the expression levels of Oct4 and Sox2, Polycomb group (PcG) proteins play a critical role in silencing developmental genes, yet the underlying mechanisms remain elusive. Yikai et al. report that PcG protein Rbbp4 represses developmental gene expression by recruiting PRC2 to the genes' promoter regions, thereby maintaining stem cell self-renewal and identity.
- Published
- 2021