TGIF2 Interacts with Histone Deacetylase 1 and Represses Transcription
Open accessAbstract
TG-interacting factor (TGIF) is a transcriptional repressor, which represses transcription by binding directly to DNA or interacts with transforming growth factor beta (TGF beta)-activated Smads, thereby repressing TGF beta-responsive gene expression. Mutation of TGIF in humans causes holoprosencephaly, a severe genetic disorder affecting craniofacial development. Searching human expressed sequence tag data bases revealed the presence of clones encoding a TGIF-related protein (TGIF2), which contains two regions of high sequence identity with TGIF. Here we show that, like TGIF, TGIF2 recruits histone deacetylase, but in contrast to TGIF, is unable to interact with the corepressor CtBP. TGIF2 and TGIF have very similar DNA-binding homeodomains, and TGIF2 represses transcription when bound to DNA via a TGIF binding site. TGIF2 interacts with TGF beta-activated Smads and represses TGF beta-responsive transcription. TGIF2 appears to be a context-independent transcriptional repressor, which can perform similar functions to TGIF and may play a role in processes, which, when disrupted by mutations in TGIF, cause holoprosencephaly.
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The TFs whose motifs overlay rs6024870 are reported to act as transcriptional repressors, such as TGIF2, HBP1, and NR1D1.
“and are reported to act as transcriptional repressors, such as TGIF262, HBP163, and NR1D164”
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- [1]1. McGinnis, W. ∙ Levine, M.S. ∙ Hafen, E. ... Nature. 1984; 308:428-433 Crossref Scopus (786) PubMed Google Scholar
- [2]2. McGinnis, W. ∙ Garber, R.L. ∙ Wirz, J. ... Cell. 1984; 37:403-408
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- Authors
- Melhuish, T. A., Gallo, C. M., & Wotton, D.
- Affiliations
- University of Virginia (US)
- Corresponding author
- Wotton, David
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-08
- Volume
- 276
- Issue
- 34
- Pages
- 32109-32114
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2158725585
- Cited by
- 137
- References
- 0
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 7 · 2023: 7 · 2022: 3 · 2021: 9 · 2020: 2 · 2019: 6 · 2018: 7 · 2017: 2 · 2016: 8 · 2015: 1 · 2014: 4 · 2013: 5 · 2012: 6
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Solar Energy Technologies Office
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- TGIF2, HDAC1, transcriptional repression, holoprosencephaly
- MeSH terms
- Amino Acid Sequence, Animals, Cell Line, Epidermal Growth Factor, Histone Deacetylases, Molecular Sequence Data, Phosphorylation, Protein Binding, Repressor Proteins, Transcription Factors, Transcription, Genetic, Signal Transduction, Transforming Growth Factor beta, Sequence Homology, Amino Acid, Homeodomain Proteins
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