TY - JOUR
T1 - WDR68 is essential for the transcriptional activation of the PRC1-AUTS2 complex and neuronal differentiation of mouse embryonic stem cells
AU - Wang, Qiang
AU - Geng, Zhuangzhuang
AU - Gong, Yi
AU - Warren, Kaitlyn
AU - Zheng, Haiyan
AU - Imamura, Yuka
AU - Gao, Zhonghua
N1 - Funding Information:
We would like to thank Dr. Sergei Grigoryev and Dr. Laura Carrel for discussions about this manuscript. We thank Dr. Irina Elcheva for the assistance in ESC characterization. This work is partially supported by a Scientist Development Award from the American Heart Association (USA) and the WW SMITH foundation (USA).
PY - 2018/12
Y1 - 2018/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.scr.2018.10.023
DO - 10.1016/j.scr.2018.10.023
M3 - Article
C2 - 30448639
AN - SCOPUS:85058448945
VL - 33
SP - 206
EP - 214
JO - Stem Cell Research
JF - Stem Cell Research
SN - 1873-5061
ER -