Maternal factor NELFA drives a 2C-like state in mouse embryonic stem cells
Autor: | Zhenhua, Hu, Dennis Eng Kiat, Tan, Gloryn, Chia, Haihan, Tan, Hwei Fen, Leong, Benjamin Jieming, Chen, Mei Sheng, Lau, Kelly Yu Sing, Tan, Xuezhi, Bi, Dongxiao, Yang, Ying Swan, Ho, Baojiang, Wu, Siqin, Bao, Esther Sook Miin, Wong, Wee-Wei, Tee |
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Rok vydání: | 2019 |
Předmět: |
Homeodomain Proteins
Male Inheritance Patterns Embryonic Development Gene Expression Regulation Developmental Cell Differentiation Mice Transgenic Mouse Embryonic Stem Cells Embryo Mammalian Chromatin Mice DNA Topoisomerases Type II Multigene Family Animals Protein Isoforms Female Poly-ADP-Ribose Binding Proteins Glycolysis Octamer Transcription Factor-3 Signal Transduction Transcription Factors |
Zdroj: | Nature cell biology. 22(2) |
ISSN: | 1476-4679 |
Popis: | Mouse embryonic stem cells (ESCs) sporadically transit into an early embryonic-like state characterized by the expression of 2-cell (2C) stage-restricted transcripts. Here, we identify a maternal factor-negative elongation factor A (NELFA)-whose heterogeneous expression in mouse ESCs is coupled to 2C gene upregulation and expanded developmental potential in vivo. We show that NELFA partners with Top2a in an interaction specific to the 2C-like state, and that it drives the expression of Dux-a key 2C regulator. Accordingly, loss of NELFA and/or Top2a suppressed Dux activation. Further characterization of 2C-like cells uncovered reduced glycolytic activity; remarkably, mere chemical suppression of glycolysis was sufficient to promote a 2C-like fate, obviating the need for genetic manipulation. Global chromatin state analysis on NELFA-induced cells revealed decommissioning of ESC-specific enhancers, suggesting ESC-state impediments to 2C reversion. Our study positions NELFA as one of the earliest drivers of the 2C-like state and illuminates factors and processes that govern this transition. |
Databáze: | OpenAIRE |
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