Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 206-214 |
| Number of pages | 9 |
| Journal | Stem Cell Research |
| Volume | 33 |
| DOIs | |
| State | Published - Dec 2018 |
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All Science Journal Classification (ASJC) codes
- Developmental Biology
- Cell Biology
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WDR68 is essential for the transcriptional activation of the PRC1-AUTS2 complex and neuronal differentiation of mouse embryonic stem cells. / Wang, Qiang; Geng, Zhuangzhuang; Gong, Yi; Warren, Kaitlyn; Zheng, Haiyan; Imamura, Yuka; Gao, Zhonghua.
In: Stem Cell Research, Vol. 33, 12.2018, p. 206-214.Research output: Contribution to journal › Article
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
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.
UR - http://www.scopus.com/inward/record.url?scp=85058448945&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058448945&partnerID=8YFLogxK
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 -