Five-Vertebrate ChIP-seq Reveals the Evolutionary Dynamics of Transcription Factor Binding
Open accessAbstract
Subtle Variation: Despite vast phenotypic differences, vertebrates have many readily recognizable specific cell types, like liver hepatocytes. The gene expression that defines specific cells depends on evolutionarily conserved orthologous transcription factors. Schmidt et al. (p. 1036 , published online 8 April) studied the conservation and divergence in the genome-wide binding of two such transcription factors, CEBPA and HNF4A, in livers from human, dog, mouse, short-tailed opossum, and chicken. Although the sequence bound by orthologous transcription factors was similar, the vast majority of binding events were unique to each species.
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Enhancer conservation is typically modular, commonly preserving the sets of binding sites for the required transcription factors, but often not their exact sequence and orientation.
“Instead, enhancer conservation is typically “modular”, commonly preserving the sets of binding sites for the required TFs, but often not their exact sequence and orientation [101–109].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [103]
The paper’s discussion (page not provided in our copy) says that tissue-specific regulation can persist through regulatory architectures independent of sequence constraint, and describes nearby compensatory TF-binding events. This supports flexibility in binding-site sequence and location, but the study examines two liver TFs and does not establish that enhancers typically preserve the full set of required TF sites or that site orientation often changes. (LLM, conf=0.85)
Experimental — accuracy not yet measuredHepatic TF cistromes can be faithfully inferred from mouse liver ChIP-seq data.
“hepatic TF cistromes can be faithfully inferred from mouse liver ChIP‐seq data (Kyrmizi et al, 2006; Schmidt et al, 2010; Dubois‐Chevalier et al, 2017a; Sommars et al, 2019; Dubois et al, 2020a).”
From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Schmidt et al, 2010
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“…polyploid cells – up to 85% in mice with mainly tetraploid hepatocytes; Dun-can et al , 2010), hepatic TF cistromes can be faithfully inferred from mouse liver ChIP-seq data (Kyrmizi et al , 2006; Schmidt et al , 2010; Dubois-Chevalier et al , 2017a; Sommars et al , 2019; Dubois et al , 2020a).”
- Authors
- Schmidt, D., Wilson, M. D., Ballester, B., Schwalie, P. C., Brown, G. D., Marshall, A., Kutter, C., Watt, S., Martinez-Jimenez, C. P., Mackay, S., Talianidis, I., Flicek, P., & Odom, D. T.
- Affiliations
- University of Cambridge (GB)
- European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
- European Bioinformatics Institute (GB)
- Cancer Research UK (GB)
- Biomedical Sciences Research Center Alexander Fleming, 16672 Vari, Greece.
- University of Glasgow (GB)
- Alexander Fleming Biomedical Sciences Research Center (GR)
- Corresponding author
- Schmidt, Dominic
- Wilson, Michael D.
- Flicek, Paul
- Odom, Duncan T.
- ORCID
- Venue
- Science
- Published
- 2010-05-21
- Volume
- 328
- Issue
- 5981
- Pages
- 1036-1040
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3008766
- OpenAlex
- W2095005830
- Cited by
- 700
- References
- 4
- Citations by year
- 2026: 15 · 2025: 13 · 2024: 19 · 2023: 19 · 2022: 28 · 2021: 31 · 2020: 25 · 2019: 25 · 2018: 43 · 2017: 38 · 2016: 41 · 2015: 68 · 2014: 64 · 2013: 84 · 2012: 76
- FWCI
- 34.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Repository of Digital Objects for Teaching Research and Culture (University of Valencia) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (079643, 062023, WT079643, WT062023)
- Cancer Research UK (15603, A15603)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- transcription factor binding, regulatory evolution, C/EBPα, liver, vertebrate evolution, species-specific binding, gene expression regulation, comparative genomics
- MeSH terms
- Algorithms, Animals, Base Sequence, Binding Sites, Chickens, DNA, Dogs, Biological Evolution, Gene Expression Regulation, Humans, Liver, Opossums, Protein Binding, Regulatory Sequences, Nucleic Acid, Species Specificity, Vertebrates, Genome, Human, Genome, Sequence Analysis, DNA, Evolution, Molecular, CCAAT-Enhancer-Binding Protein-alpha, Chromatin Immunoprecipitation, Mice, Hepatocyte Nuclear Factor 4
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