WDR68 is essential for the transcriptional activation of the PRC1-AUTS2 complex and neuronal differentiation of mouse embryonic stem cells - ScienceDirect

Stem Cell Research

Yi Gong^2¹  Qiang Wang^1²  Kaitlyn Warren^1³  Zhuangzhuang Geng^1⁴  Haiyan Zheng^3⁵  Yuka Imamura^1,4⁶ 

[1] Biological Mass Spectrometry Facility at Robert Wood Johnson Medical School and Rutgers, The State University of New, Piscataway, NJ 08854, Jersey,^3;Departments of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, PA 17033, United States^1;Departments of Pharmacology and Institute for Personalized Medicine, Penn State College of Medicine, Hershey, PA 17033, United States^4;National Institute on Aging, Bethesda, MD 20892, United States^2;Penn State Hershey Cancer Institute, Hershey, PA 17033, United States^5;The Stem Cell and Regenerative Biology Program^6

关键词: Epigenetics;    Stem cells;    Transcription;    Polycomb;    Protein complex;    Differentiation;   

DOI  :  10.1016/j.scr.2018.10.023

学科分类：生物科学（综合）

来源: Elsevier

【 摘 要 】

Recent studies on Polycomb repressive complexes (PRC) reveal a surprising role in transcriptional activation, yet the underlying mechanism remains poorly understood. We previously identified a type 1 PRC (PRC1) that contains Autism Susceptibility Candidate 2 (AUTS2), which positively regulates transcription of neuronal genes. However, the mechanism by which the PRC1-AUTS2 complex influences neurodevelopment is unclear. Here we demonstrate that WDR68 is not only an integral component of the PRC1-AUTS2 complex, but it is also required for PRC1-AUTS2-mediated transcription activation. Furthermore, deletion of Wdr68 in mouse embryonic stem cells leads to defects in neuronal differentiation without affecting self-renewal. Through transcriptomic analysis, we found that many genes responsible for neuronal differentiation are down-regulated in Wdr68 deficient neural progenitors. These genes include those targeted by the PRC1-AUTS2 complex. In summary, our studies uncovered a previously unknown but essential component of the active PRC1 complex and evidence of its role in regulating the expression of genes that are important for neuronal differentiation.

【 授权许可】

Unknown