Tissue-specific transcriptional regulation has diverged significantly between human and mouse
Open accessAbstract
We demonstrate that the binding sites for highly conserved transcription factors vary extensively between human and mouse. We mapped the binding of four tissue-specific transcription factors (FOXA2, HNF1A, HNF4A and HNF6) to 4,000 orthologous gene pairs in hepatocytes purified from human and mouse livers. Despite the conserved function of these factors, from 41% to 89% of their binding events seem to be species specific. When the same protein binds the promoters of orthologous genes, approximately two-thirds of the binding sites do not align.
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Despite decades of using animal models, not a single neuroprotective agent that ameliorated spinal cord injury in animal tests has proven efficacious in clinical trials to date.
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- Authors
- Odom, D. T., Dowell, R. D., Jacobsen, E. S., Gordon, W., Danford, T. W., MacIsaac, K. D., Rolfe, P. A., Conboy, C. M., Gifford, D. K., & Fraenkel, E.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- MIT Computer Science and Artificial Intelligence Laboratory (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Fraenkel, Ernest
- Venue
- Nature Genetics
- Published
- 2007-05-21
- Volume
- 39
- Issue
- 6
- Pages
- 730-732
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3797512
- OpenAlex
- W1988871238
- Cited by
- 506
- References
- 16
- Citations by year
- 2026: 9 · 2025: 5 · 2024: 12 · 2023: 10 · 2022: 12 · 2021: 14 · 2020: 6 · 2019: 11 · 2018: 17 · 2017: 26 · 2016: 15 · 2015: 36 · 2014: 41 · 2013: 29 · 2012: 43
- FWCI
- 22.63
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Cancer Research UK (15603, A15603)
- National Institutes of Health (n01dk092310-000)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK068655, K25DK070813, DK70813, DK076284, DK-92310, F32DK076284, DK-68655)
- U.S. National Library of Medicine (N01 DK092310)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- tissue-specific transcription factors, human-mouse divergence, FOXA2, HNF1A, HNF4α, HNF6, transcription factor binding sites, orthologs, hepatocytes, liver, promoter binding
- MeSH terms
- Animals, Gene Expression Regulation, Humans, Regulatory Sequences, Nucleic Acid, Transcription Factors, Transcription, Genetic, Genetic Variation, Conserved Sequence, Sequence Homology, Mice, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 3-beta, Hepatocyte Nuclear Factor 4, Hepatocyte Nuclear Factor 6
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