Dissecting Oct3/4-regulated gene networks in embryonic stem cells by expression profiling

Ryo Matoba, Hitoshi Niwa, Shinji Masui, Satoshi Ohtsuka, Mark G. Carter, Alexei A. Sharov, Minoru Ko

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

POU transcription factor Pou5f1 (Oct3/4) is required to maintain ES cells in an undifferentiated state. Here we show that global expression profiling of Oct3/4-manipulated ES cells delineates the downstream target genes of Oct3/4. Combined with data from genome-wide chromatin-immunoprecipitation (ChIP) assays, this analysis identifies not only primary downstream targets of Oct3/4, but also secondary or tertiary targets. Furthermore, the analysis also reveals that downstream target genes are regulated either positively or negatively by Oct3/4. Identification of a group of genes that show both activation and repression depending on Oct3/4 expression levels provides a possible mechanism for the requirement of appropriate Oct3/4 expression to maintain undifferentiated ES cells. As a proof-of-principle study, one of the downstream genes, Tcl1, has been analyzed in detail. We show that Oct3/4 binds to the promoter region of Tcl1 and activates its transcription. We also show that Tcl1 is involved in the regulation of proliferation, but not differentiation, in ES cells. These findings suggest that the global expression profiling of gene-manipulated ES cells can help to delineate the structure and dynamics of gene regulatory networks.

Original languageEnglish
Article numbere26
JournalPLoS One
Volume1
Issue number1
DOIs
Publication statusPublished - 2006 Dec 20
Externally publishedYes

Fingerprint

Gene Regulatory Networks
embryonic stem cells
Embryonic Stem Cells
Stem cells
Genes
genes
POU Domain Factors
cells
Social Identification
Chromatin Immunoprecipitation
Gene Expression Profiling
Genetic Promoter Regions
cell differentiation
chromatin
transcription factors
transcription (genetics)
Transcription
promoter regions
gene regulatory networks
Genome

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Dissecting Oct3/4-regulated gene networks in embryonic stem cells by expression profiling. / Matoba, Ryo; Niwa, Hitoshi; Masui, Shinji; Ohtsuka, Satoshi; Carter, Mark G.; Sharov, Alexei A.; Ko, Minoru.

In: PLoS One, Vol. 1, No. 1, e26, 20.12.2006.

Research output: Contribution to journalArticle

Matoba, Ryo ; Niwa, Hitoshi ; Masui, Shinji ; Ohtsuka, Satoshi ; Carter, Mark G. ; Sharov, Alexei A. ; Ko, Minoru. / Dissecting Oct3/4-regulated gene networks in embryonic stem cells by expression profiling. In: PLoS One. 2006 ; Vol. 1, No. 1.
@article{382b65a47a8947599950dd0266084787,
title = "Dissecting Oct3/4-regulated gene networks in embryonic stem cells by expression profiling",
abstract = "POU transcription factor Pou5f1 (Oct3/4) is required to maintain ES cells in an undifferentiated state. Here we show that global expression profiling of Oct3/4-manipulated ES cells delineates the downstream target genes of Oct3/4. Combined with data from genome-wide chromatin-immunoprecipitation (ChIP) assays, this analysis identifies not only primary downstream targets of Oct3/4, but also secondary or tertiary targets. Furthermore, the analysis also reveals that downstream target genes are regulated either positively or negatively by Oct3/4. Identification of a group of genes that show both activation and repression depending on Oct3/4 expression levels provides a possible mechanism for the requirement of appropriate Oct3/4 expression to maintain undifferentiated ES cells. As a proof-of-principle study, one of the downstream genes, Tcl1, has been analyzed in detail. We show that Oct3/4 binds to the promoter region of Tcl1 and activates its transcription. We also show that Tcl1 is involved in the regulation of proliferation, but not differentiation, in ES cells. These findings suggest that the global expression profiling of gene-manipulated ES cells can help to delineate the structure and dynamics of gene regulatory networks.",
author = "Ryo Matoba and Hitoshi Niwa and Shinji Masui and Satoshi Ohtsuka and Carter, {Mark G.} and Sharov, {Alexei A.} and Minoru Ko",
year = "2006",
month = "12",
day = "20",
doi = "10.1371/journal.pone.0000026",
language = "English",
volume = "1",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - Dissecting Oct3/4-regulated gene networks in embryonic stem cells by expression profiling

AU - Matoba, Ryo

AU - Niwa, Hitoshi

AU - Masui, Shinji

AU - Ohtsuka, Satoshi

AU - Carter, Mark G.

AU - Sharov, Alexei A.

AU - Ko, Minoru

PY - 2006/12/20

Y1 - 2006/12/20

N2 - POU transcription factor Pou5f1 (Oct3/4) is required to maintain ES cells in an undifferentiated state. Here we show that global expression profiling of Oct3/4-manipulated ES cells delineates the downstream target genes of Oct3/4. Combined with data from genome-wide chromatin-immunoprecipitation (ChIP) assays, this analysis identifies not only primary downstream targets of Oct3/4, but also secondary or tertiary targets. Furthermore, the analysis also reveals that downstream target genes are regulated either positively or negatively by Oct3/4. Identification of a group of genes that show both activation and repression depending on Oct3/4 expression levels provides a possible mechanism for the requirement of appropriate Oct3/4 expression to maintain undifferentiated ES cells. As a proof-of-principle study, one of the downstream genes, Tcl1, has been analyzed in detail. We show that Oct3/4 binds to the promoter region of Tcl1 and activates its transcription. We also show that Tcl1 is involved in the regulation of proliferation, but not differentiation, in ES cells. These findings suggest that the global expression profiling of gene-manipulated ES cells can help to delineate the structure and dynamics of gene regulatory networks.

AB - POU transcription factor Pou5f1 (Oct3/4) is required to maintain ES cells in an undifferentiated state. Here we show that global expression profiling of Oct3/4-manipulated ES cells delineates the downstream target genes of Oct3/4. Combined with data from genome-wide chromatin-immunoprecipitation (ChIP) assays, this analysis identifies not only primary downstream targets of Oct3/4, but also secondary or tertiary targets. Furthermore, the analysis also reveals that downstream target genes are regulated either positively or negatively by Oct3/4. Identification of a group of genes that show both activation and repression depending on Oct3/4 expression levels provides a possible mechanism for the requirement of appropriate Oct3/4 expression to maintain undifferentiated ES cells. As a proof-of-principle study, one of the downstream genes, Tcl1, has been analyzed in detail. We show that Oct3/4 binds to the promoter region of Tcl1 and activates its transcription. We also show that Tcl1 is involved in the regulation of proliferation, but not differentiation, in ES cells. These findings suggest that the global expression profiling of gene-manipulated ES cells can help to delineate the structure and dynamics of gene regulatory networks.

UR - http://www.scopus.com/inward/record.url?scp=55149099432&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55149099432&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0000026

DO - 10.1371/journal.pone.0000026

M3 - Article

VL - 1

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e26

ER -