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Cited by 184Pluripotent Stem Cells ResearchGenomics and Chromatin DynamicsEpigenetics and DNA Methylation

Stat3 and c-Myc genome-wide promoter occupancy in embryonic stem cells

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Kidder, Benjamin L., Yang, Jim, Palmer, Stephen·2008·PLoS ONE
DOI 10.1371/journal.pone.0003932PMC PMC2592696
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Abstract

Embryonic stem (ES) cell pluripotency is regulated in part by transcription factor (TF) pathways that maintain self-renewal and inhibit differentiation. Stat3 and c-Myc TFs are essential for maintaining mouse ES cell self-renewal. c-Myc, together with Oct4, Sox2, and Klf4, is a reprogramming factor. While previous studies have investigated core transcriptional circuitry in ES cells, other TF pathways that promote ES cell pluripotency have yet to be investigated. Therefore, to further understand ES cell transcriptional networks, we used genome-wide chromatin immunoprecipitation and microarray analysis (ChIP-chip) to map Stat3 and c-Myc binding targets in ES cells. Our results show that Stat3 and c-Myc occupy a significant number of genes whose expression is highly enriched in ES cells. By comparing Stat3 and c-Myc target genes with gene expression data from undifferentiated ES cells and embryoid bodies (EBs), we found that Stat3 binds active and inactive genes in ES cells, while c-Myc binds predominantly active genes. Moreover, the transcriptional states of Stat3 and c-Myc targets are correlated with co-occupancy of pluripotency-related TFs, polycomb group proteins, and active and repressive histone modifications. We also provide evidence that Stat3 targets are differentially expressed in ES cells following removal of LIF, where culture of ES cells in the absence of LIF resulted in downregulation of Stat3 target genes enriched in ES cells, and upregulation of lineage specific Stat3 target genes. Altogether, we reveal transcriptional targets of two key pluripotency-related genes in ES cells--Stat3 and c-Myc, thus providing further insight into the ES cell transcriptional network.

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References 49 · Cited by 184

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Authors
Kidder, B. L., Yang, J., & Palmer, S.
Affiliations
EMD Serono, Inc. (United States) (US)
Corresponding author
Kidder, Benjamin L.
ORCID
Kidder, Benjamin L.
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2008-12-11
Volume
3
Issue
12
Pages
e3932
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0003932
PMC
PMC2592696
OpenAlex
W2038121225
Cited by
184
References
49
Citations by year
2025: 3 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 8 · 2020: 2 · 2019: 1 · 2018: 9 · 2017: 9 · 2016: 6 · 2015: 13 · 2014: 14 · 2013: 20 · 2012: 20
FWCI
8.92
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
EMD Serono
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
STAT3, c-Myc, embryonic stem cells, pluripotency, transcription factor binding sites, promoter binding, self-renewal, lineage specification, histone modifications, Polycomb group proteins, transcriptional regulatory networks, embryoid bodies
MeSH terms
Kruppel-Like Factor 4, Animals, Cells, Cultured, Histones, Promoter Regions, Genetic, Protein Binding, Protein Processing, Post-Translational, Repressor Proteins, Transcription Factors, Proto-Oncogene Proteins c-myc, Genome, Gene Expression Regulation, Developmental, Cell Lineage, Gene Expression Profiling, Pluripotent Stem Cells, Chromatin Immunoprecipitation, STAT3 Transcription Factor, Mice, Embryonic Stem Cells, Leukemia Inhibitory Factor

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