Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells.
Joon-Lin Chew,Yuin-Han Loh,Yuin-Han Loh,Wensheng Zhang,Xi Chen,Xi Chen,Wai Leong Tam,Leng-Siew Yeap,Pin Li,Yen-Sin Ang,Bing Lim,Bing Lim,Paul Robson,Paul Robson,Huck-Hui Ng,Huck-Hui Ng +15 more
TLDR
A positive and potentially self-reinforcing regulatory loop that maintains Pou5f1 and Sox2 expression via the Oct4/Sox2 complex in pluripotent cells is uncovered.Abstract:
Embryonic stem cells (ESCs) are pluripotent cells that can either self-renew or differentiate into many cell types. Oct4 and Sox2 are transcription factors essential to the pluripotent and self-renewing phenotypes of ESCs. Both factors are upstream in the hierarchy of the transcription regulatory network and are partners in regulating several ESC-specific genes. In ESCs, Sox2 is transcriptionally regulated by an enhancer containing a composite sox-oct element that Oct4 and Sox2 bind in a combinatorial interaction. It has previously been shown that Pou5f1, the Oct4 gene, contains a distal enhancer imparting specific expression in both ESCs and preimplantation embryos. Here, we identify a composite sox-oct element within this enhancer and show that it is involved in Pou5f1 transcriptional activity in ESCs. In vitro experiments with ESC nuclear extracts demonstrate that Oct4 and Sox2 interact specifically with this regulatory element. More importantly, by chromatin immunoprecipitation assay, we establish that both Oct4 and Sox2 bind directly to the composite sox-oct elements in both Pou5f1 and Sox2 in living mouse and human ESCs. Specific knockdown of either Oct4 or Sox2 by RNA interference leads to the reduction of both genes' enhancer activities and endogenous expression levels in addition to ESC differentiation. Our data uncover a positive and potentially self-reinforcing regulatory loop that maintains Pou5f1 and Sox2 expression via the Oct4/Sox2 complex in pluripotent cells.read more
Citations
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Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells
Xi Chen,Han Xu,Ping Yuan,Fang Fang,Fang Fang,Mikael Huss,Vinsensius B. Vega,Eleanor Wong,Yuriy L. Orlov,Weiwei Zhang,Weiwei Zhang,Jianming Jiang,Jianming Jiang,Yuin-Han Loh,Yuin-Han Loh,Hock Chuan Yeo,Zhen Xuan Yeo,Vipin Narang,Kunde R Govindarajan,Bernard Leong,Atif Shahab,Yijun Ruan,Guillaume Bourque,Wing-Kin Sung,Neil D. Clarke,Chia-Lin Wei,Huck-Hui Ng,Huck-Hui Ng +27 more
TL;DR: This study uses chromatin immunoprecipitation coupled with ultra-high-throughput DNA sequencing to map the locations of TF-binding sites and identifies important features of the transcriptional regulatory networks that define ES-cell identity.
Journal ArticleDOI
The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells.
Yuin-Han Loh,Qiang Wu,Joon Lin Chew,Joon Lin Chew,Vinsensius B. Vega,Weiwei Zhang,Weiwei Zhang,Xi Chen,Xi Chen,Guillaume Bourque,Joshy George,Bernard Leong,Jun Liu,Kee Yew Wong,Ken W. Sung,Charlie W.H. Lee,Xiao Dong Zhao,Kuo Ping Chiu,Leonard Lipovich,Vladimir A. Kuznetsov,Paul Robson,Paul Robson,Lawrence W. Stanton,Chia-Lin Wei,Yijun Ruan,Bing Lim,Bing Lim,Huck-Hui Ng,Huck-Hui Ng +28 more
TL;DR: By integrating RNA interference–mediated depletion of Oct4 and Nanog with microarray expression profiling, it is demonstrated that these factors can activate or suppress transcription, and it is shown that common core downstream targets are important to keep ES cells from differentiating.
Journal ArticleDOI
Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells
Shinji Masui,Yuhki Nakatake,Yayoi Toyooka,Daisuke Shimosato,Rika Yagi,Kazue Takahashi,Hitoshi Okochi,Akihiko Okuda,Ryo Matoba,Alexei A. Sharov,Minoru S.H. Ko,Hitoshi Niwa +11 more
TL;DR: The results indicate that the essential function of Sox2 is to stabilize ES cells in a pluripotent state by maintaining the requisite level of Oct3/4 expression.
Journal ArticleDOI
Distinct Factors Control Histone Variant H3.3 Localization at Specific Genomic Regions
Aaron D Goldberg,Laura A. Banaszynski,Kyung-Min Noh,Peter W. Lewis,Simon J. Elsaesser,Sonja C. Stadler,Scott Dewell,Martin J. Law,Xingyi Guo,Xuan Li,Duancheng Wen,Duancheng Wen,Ariane Chapgier,Russell Dekelver,Jeffrey C. Miller,Ya Li Lee,Elizabeth A. Boydston,Michael C. Holmes,Philip D. Gregory,John M. Greally,Shahin Rafii,Shahin Rafii,Chingwen Yang,Peter J. Scambler,David Garrick,Richard J. Gibbons,Douglas R. Higgs,Ileana M. Cristea,Fyodor D. Urnov,Deyou Zheng,C. David Allis +30 more
TL;DR: It is demonstrated that multiple and distinct factors are responsible for H3.3 localization at specific genomic locations in mammalian cells.
Journal ArticleDOI
Control of the Embryonic Stem Cell State
TL;DR: This work has provided insights into the transcriptional control of embryonic stem cell state, including the regulatory circuitry underlying pluripotency and uncovered fundamental mechanisms that control mammalian gene expression, connect gene expression to chromosome structure, and contribute to human disease.
References
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