Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells
Open accessAbstract
The transcription factors OCT4, SOX2, and NANOG have essential roles in early development and are required for the propagation of undifferentiated embryonic stem (ES) cells in culture. To gain insights into transcriptional regulation of human ES cells, we have identified OCT4, SOX2, and NANOG target genes using genome-scale location analysis. We found, surprisingly, that OCT4, SOX2, and NANOG co-occupy a substantial portion of their target genes. These target genes frequently encode transcription factors, many of which are developmentally important homeodomain proteins. Our data also indicate that OCT4, SOX2, and NANOG collaborate to form regulatory circuitry consisting of autoregulatory and feedforward loops. These results provide new insights into the transcriptional regulation of stem cells and reveal how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal.
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Core transcriptional regulatory circuitries self-sustain high expression of identity transcription factors and their target effector genes and are involved in continuous modulation of the hepatic transcriptome in response to environmental stimuli.
“Indeed, CoRCs allows to self‐sustain high expression of identity TFs and their target effector genes in addition to being involved in the continuous modulation of the hepatic transcriptome in response to environmental stimuli (Boyer et al, 2005; Arendt et al, 2016; Wilkinson et al, 2017; Almeida et al, 2021).”
From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Boyer et al, 2005
In mice and humans, pioneer factors OCT4 and SOX2 form a core part of the regulatory network controlling stem cell pluripotency.
“In mice and humans, the pioneer factors OCT4 and SOX2 form a core part of the regulatory network controlling stem cell pluripotency [36].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [36]
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- Authors
- Boyer, L. A., Lee, T. I., Cole, M. F., Johnstone, S. E., Levine, S. S., Zucker, J. P., Guenther, M. G., Kumar, R. M., Murray, H. L., Jenner, R. G., Gifford, D. K., Melton, D. A., Jaenisch, R., & Young, R. A.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Howard Hughes Medical Institute (US)
- Broad Institute (US)
- Corresponding author
- Young, Richard A.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2005-09
- Volume
- 122
- Issue
- 6
- Pages
- 947-956
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3006442
- OpenAlex
- W2107575419
- Cited by
- 4,505
- References
- 0
- Citations by year
- 2026: 78 · 2025: 86 · 2024: 89 · 2023: 130 · 2022: 143 · 2021: 172 · 2020: 196 · 2019: 194 · 2018: 205 · 2017: 220 · 2016: 223 · 2015: 249 · 2014: 266 · 2013: 313 · 2012: 352
- FWCI
- 77.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Human Genome Research Institute (HG002668, R01HG002668)
- National Cancer Institute (CA094664, F32CA094664)
- National Institute of General Medical Sciences (GM068273, R01GM069400, F32GM068273, GM069400)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- human embryonic stem cells, Oct4, SOX2, Nanog, transcription factor target genes, homeodomain transcription factor, autoregulatory loop, feed-forward loop, pluripotency, self-renewal
- MeSH terms
- Nanog Homeobox Protein, Animals, Cell Differentiation, Cells, Cultured, DNA-Binding Proteins, Embryo, Mammalian, Genes, Regulator, Humans, Promoter Regions, Genetic, Protein Binding, Stem Cells, Transcription Factors, Signal Transduction, Cell Transplantation, Homeodomain Proteins, Gene Expression Regulation, Developmental, Oligonucleotide Array Sequence Analysis, HMGB Proteins, MicroRNAs, Octamer Transcription Factor-3, Mice, SOXB1 Transcription Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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