ArticlePLoS computational biology2011
Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.
Article in PLoS computational biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 59 citations in OpenAlex.
- Enhancer-based gene therapy: a new path for precision medicine.Hereditas · 2026Review
- "Stem Cells in Regenerative Medicine: from Discovery and Molecular Mechanisms To Therapeutic Applications and Clinical Challenges".Cell biochemistry and biophysics · 2026Review
- Proteogenomic reprogramming to a functional human blastomere-like stem cell state via a PARP-DUX4 regulatory axis.Cell reports · 2025Article
- Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis.Developmental cell · 2025Article
- Rise and SINE: roles of transcription factors and retrotransposons in zygotic genome activation.Nature reviews. Molecular cell biology · 2025Article
- Identification of transcription factor co-binding patterns with non-negative matrix factorization.Nucleic acids research · 2024Article
- Article
- Low complexity domains, condensates, and stem cell pluripotency.World journal of stem cells · 2021Review
- Accessible chromatin reveals regulatory mechanisms underlying cell fate decisions during early embryogenesis.Scientific reports · 2021Article
- Differential transcriptional regulation of the NANOG gene in chicken primordial germ cells and embryonic stem cells.Journal of animal science and biotechnology · 2021Article
- Organization of the Pluripotent Genome.Cold Spring Harbor perspectives in biology · 2021Review
- Constructing temporal regulatory cascades in the context of development and cell differentiation.PloS one · 2020Article
- Differential analysis of combinatorial protein complexes with CompleXChange.BMC bioinformatics · 2019Article
- Network Medicine in the Age of Biomedical Big Data.Frontiers in genetics · 2019Review
- AIMP3 depletion causes genome instability and loss of stemness in mouse embryonic stem cells.Cell death & disease · 2018Article
- Transposable Element Mediated Innovation in Gene Regulatory Landscapes of Cells: Re-Visiting the "Gene-Battery" Model.BioEssays : news and reviews in molecular, cellular and developmental biology · 2018Review
- NANOG Plays a Hierarchical Role in the Transcription Network Regulating the Pluripotency and Plasticity of Adipose Tissue-Derived Stem Cells.International journal of molecular sciences · 2017Article
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- Article
- CTRL+INSERT: retrotransposons and their contribution to regulation and innovation of the transcriptome.EMBO reports · 2016Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcription factors are proteins that regulate gene expression by binding to cis-regulatory sequences such as promoters and enhancers. In embryonic stem (ES) cells, binding of the transcription factors OCT4, SOX2 and NANOG is essential to maintain the capacity of the cells to differentiate into any cell type of the developing embryo. It is known that transcription factors interact to regulate gene expression. In this study we show that combinatorial binding is strongly associated with co-localization of the transcriptional co-activator Mediator, H3K27ac and increased expression of nearby genes in embryonic stem cells. We observe that the same loci bound by Oct4, Nanog and Sox2 in ES cells frequently drive expression in early embryonic development. Comparison of mouse and human ES cells shows that less than 5% of individual binding events for OCT4, SOX2 and NANOG are shared between species. In contrast, about 15% of combinatorial binding events and even between 53% and 63% of combinatorial binding events at enhancers active in early development are conserved. Our analysis suggests that the combination of OCT4, SOX2 and NANOG binding is critical for transcription in ES cells and likely plays an important role for embryogenesis by binding at conserved early developmental enhancers. Our data suggests that the fast evolutionary rewiring of regulatory networks mainly affects individual binding events, whereas "gene regulatory hotspots" which are bound by multiple factors and active in multiple tissues throughout early development are under stronger evolutionary constraints.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.