Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells

Xi Chen; Han Xu; Ping Yuan; Fang Fang; Mikael Huss; Vinsensius B. Vega; Eleanor Wong; Yuriy L. Orlov; Weiwei Zhang; Jianming Jiang; Yuin Han Loh; Hock Chuan Yeo; Zhen Xuan Yeo; Vipin Narang; Kunde Ramamoorthy Govindarajan; Bernard Leong; Atif Shahab; Yijun Ruan; Guillaume Bourque; Wing Kin Sung; Neil D. Clarke; Chia Lin Wei; Huck Hui Ng

doi:10.1016/j.cell.2008.04.043

Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells

Xi Chen, Han Xu, Ping Yuan, Fang Fang, Mikael Huss, Vinsensius B. Vega, Eleanor Wong, Yuriy L. Orlov, Weiwei Zhang, Jianming Jiang, Yuin Han Loh, Hock Chuan Yeo, Zhen Xuan Yeo, Vipin Narang, Kunde Ramamoorthy Govindarajan, Bernard Leong, Atif Shahab, Yijun Ruan, Guillaume Bourque, Wing Kin SungNeil D. Clarke, Chia Lin Wei, Huck Hui Ng

Research output: Contribution to journal › Article › peer-review

2011 Scopus citations

Abstract

Transcription factors (TFs) and their specific interactions with targets are crucial for specifying gene-expression programs. To gain insights into the transcriptional regulatory networks in embryonic stem (ES) cells, we use chromatin immunoprecipitation coupled with ultra-high-throughput DNA sequencing (ChIP-seq) to map the locations of 13 sequence-specific TFs (Nanog, Oct4, STAT3, Smad1, Sox2, Zfx, c-Myc, n-Myc, Klf4, Esrrb, Tcfcp2l1, E2f1, and CTCF) and 2 transcription regulators (p300 and Suz12). These factors are known to play different roles in ES-cell biology as components of the LIF and BMP signaling pathways, self-renewal regulators, and key reprogramming factors. Our study provides insights into the integration of the signaling pathways into the ES-cell-specific transcription circuitries. Intriguingly, we find specific genomic regions extensively targeted by different TFs. Collectively, the comprehensive mapping of TF-binding sites identifies important features of the transcriptional regulatory networks that define ES-cell identity.

Original language	English (US)
Pages (from-to)	1106-1117
Number of pages	12
Journal	Cell
Volume	133
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2008.04.043
State	Published - Jun 13 2008
Externally published	Yes

Keywords

DNA
PROTEINS
STEMCELL

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2008.04.043

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Chen, X., Xu, H., Yuan, P., Fang, F., Huss, M., Vega, V. B., Wong, E., Orlov, Y. L., Zhang, W., Jiang, J., Loh, Y. H., Yeo, H. C., Yeo, Z. X., Narang, V., Govindarajan, K. R., Leong, B., Shahab, A., Ruan, Y., Bourque, G., ... Ng, H. H. (2008). Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells. Cell, 133(6), 1106-1117. https://doi.org/10.1016/j.cell.2008.04.043

Chen, X, Xu, H, Yuan, P, Fang, F, Huss, M, Vega, VB, Wong, E, Orlov, YL, Zhang, W, Jiang, J, Loh, YH, Yeo, HC, Yeo, ZX, Narang, V, Govindarajan, KR, Leong, B, Shahab, A, Ruan, Y, Bourque, G, Sung, WK, Clarke, ND, Wei, CL & Ng, HH 2008, 'Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells', Cell, vol. 133, no. 6, pp. 1106-1117. https://doi.org/10.1016/j.cell.2008.04.043

@article{e4661a4b5c684068bd26614c8b612d04,

title = "Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells",

abstract = "Transcription factors (TFs) and their specific interactions with targets are crucial for specifying gene-expression programs. To gain insights into the transcriptional regulatory networks in embryonic stem (ES) cells, we use chromatin immunoprecipitation coupled with ultra-high-throughput DNA sequencing (ChIP-seq) to map the locations of 13 sequence-specific TFs (Nanog, Oct4, STAT3, Smad1, Sox2, Zfx, c-Myc, n-Myc, Klf4, Esrrb, Tcfcp2l1, E2f1, and CTCF) and 2 transcription regulators (p300 and Suz12). These factors are known to play different roles in ES-cell biology as components of the LIF and BMP signaling pathways, self-renewal regulators, and key reprogramming factors. Our study provides insights into the integration of the signaling pathways into the ES-cell-specific transcription circuitries. Intriguingly, we find specific genomic regions extensively targeted by different TFs. Collectively, the comprehensive mapping of TF-binding sites identifies important features of the transcriptional regulatory networks that define ES-cell identity.",

keywords = "DNA, PROTEINS, STEMCELL",

author = "Xi Chen and Han Xu and Ping Yuan and Fang Fang and Mikael Huss and Vega, {Vinsensius B.} and Eleanor Wong and Orlov, {Yuriy L.} and Weiwei Zhang and Jianming Jiang and Loh, {Yuin Han} and Yeo, {Hock Chuan} and Yeo, {Zhen Xuan} and Vipin Narang and Govindarajan, {Kunde Ramamoorthy} and Bernard Leong and Atif Shahab and Yijun Ruan and Guillaume Bourque and Sung, {Wing Kin} and Clarke, {Neil D.} and Wei, {Chia Lin} and Ng, {Huck Hui}",

note = "Funding Information: This work is supported by the Agency for Science, Technology and Research (A ∗ STAR) of Singapore, Singapore Stem Cell Consortium grant (to H.H.N) and the NIH ENCODE grant 1R01HG003521-01 (to Y. R and C.L.W). X.C, W.Z, and J.M.J are supported by the National University of Singapore graduate scholarships. We thank Andrew Hutchins, Ching-Aeng Lim, Edwin Chueng and Feng Lin for critical comments on the manuscript. We are grateful to Katty Kuay and Qiu-Li Tan for technical assistance. ",

year = "2008",

month = jun,

day = "13",

doi = "10.1016/j.cell.2008.04.043",

language = "English (US)",

volume = "133",

pages = "1106--1117",

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T1 - Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells

AU - Chen, Xi

AU - Xu, Han

AU - Yuan, Ping

AU - Fang, Fang

AU - Huss, Mikael

AU - Vega, Vinsensius B.

AU - Wong, Eleanor

AU - Orlov, Yuriy L.

AU - Zhang, Weiwei

AU - Jiang, Jianming

AU - Loh, Yuin Han

AU - Yeo, Hock Chuan

AU - Yeo, Zhen Xuan

AU - Narang, Vipin

AU - Govindarajan, Kunde Ramamoorthy

AU - Leong, Bernard

AU - Shahab, Atif

AU - Ruan, Yijun

AU - Bourque, Guillaume

AU - Sung, Wing Kin

AU - Clarke, Neil D.

AU - Wei, Chia Lin

AU - Ng, Huck Hui

N1 - Funding Information: This work is supported by the Agency for Science, Technology and Research (A ∗ STAR) of Singapore, Singapore Stem Cell Consortium grant (to H.H.N) and the NIH ENCODE grant 1R01HG003521-01 (to Y. R and C.L.W). X.C, W.Z, and J.M.J are supported by the National University of Singapore graduate scholarships. We thank Andrew Hutchins, Ching-Aeng Lim, Edwin Chueng and Feng Lin for critical comments on the manuscript. We are grateful to Katty Kuay and Qiu-Li Tan for technical assistance.

PY - 2008/6/13

Y1 - 2008/6/13

N2 - Transcription factors (TFs) and their specific interactions with targets are crucial for specifying gene-expression programs. To gain insights into the transcriptional regulatory networks in embryonic stem (ES) cells, we use chromatin immunoprecipitation coupled with ultra-high-throughput DNA sequencing (ChIP-seq) to map the locations of 13 sequence-specific TFs (Nanog, Oct4, STAT3, Smad1, Sox2, Zfx, c-Myc, n-Myc, Klf4, Esrrb, Tcfcp2l1, E2f1, and CTCF) and 2 transcription regulators (p300 and Suz12). These factors are known to play different roles in ES-cell biology as components of the LIF and BMP signaling pathways, self-renewal regulators, and key reprogramming factors. Our study provides insights into the integration of the signaling pathways into the ES-cell-specific transcription circuitries. Intriguingly, we find specific genomic regions extensively targeted by different TFs. Collectively, the comprehensive mapping of TF-binding sites identifies important features of the transcriptional regulatory networks that define ES-cell identity.

AB - Transcription factors (TFs) and their specific interactions with targets are crucial for specifying gene-expression programs. To gain insights into the transcriptional regulatory networks in embryonic stem (ES) cells, we use chromatin immunoprecipitation coupled with ultra-high-throughput DNA sequencing (ChIP-seq) to map the locations of 13 sequence-specific TFs (Nanog, Oct4, STAT3, Smad1, Sox2, Zfx, c-Myc, n-Myc, Klf4, Esrrb, Tcfcp2l1, E2f1, and CTCF) and 2 transcription regulators (p300 and Suz12). These factors are known to play different roles in ES-cell biology as components of the LIF and BMP signaling pathways, self-renewal regulators, and key reprogramming factors. Our study provides insights into the integration of the signaling pathways into the ES-cell-specific transcription circuitries. Intriguingly, we find specific genomic regions extensively targeted by different TFs. Collectively, the comprehensive mapping of TF-binding sites identifies important features of the transcriptional regulatory networks that define ES-cell identity.

KW - DNA

KW - PROTEINS

KW - STEMCELL

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DO - 10.1016/j.cell.2008.04.043

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AN - SCOPUS:44649117905

SN - 0092-8674

VL - 133

SP - 1106

EP - 1117

JO - Cell

JF - Cell

IS - 6

ER -

Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells

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Keywords

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