Pbx Marks Genes for Activation by MyoD Indicating a Role for a Homeodomain Protein in Establishing Myogenic Potential
Open accessAbstract
Skeletal muscle differentiation is initiated by the transcription factor MyoD, which binds directly to the regulatory regions of genes expressed during skeletal muscle differentiation and initiates chromatin remodeling at specific promoters. It is not known, however, how MyoD initially recognizes its binding site in a chromatin context. Here we show that the H/C and helix III domains, two domains of MyoD that are necessary for the initiation of chromatin remodeling at the myogenin locus, together regulate a restricted subset of genes, including myogenin. These domains are necessary for the stable binding of MyoD to the myogenin promoter through an interaction with an adjacent protein complex containing the homeodomain protein Pbx, which appears to be constitutively bound at this site. This demonstrates a specific mechanism of targeting MyoD to loci in inactive chromatin and reveals a critical role of homeodomain proteins in marking specific genes for activation in the muscle lineage.
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PBX1 can bind closed chromatin.
“PDX1 does, though, interact with PBX1 (Liu et al. 2001;Oliver-Krasinski et al. 2009), which can bind closed chromatin (Berkes et al. 2004), and it is possible that these sites represent pioneer activity of one of PDX1's binding partners.”
From Locus co-occupancy, nucleosome positioning, and H3K4me1 regulate the functionality of FOXA2-, HNF4A-, and PDX1-bound loci in islets and liver (2010) · cites this paper as Berkes et al. 2004
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“chromatin (Berkes et al. 2004), and it is possible that these sites Hoffman et al.”
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- Authors
- Berkes, C. A., Bergstrom, D. A., Penn, B. H., Seaver, K. J., Knoepfler, P. S., & Tapscott, S. J.
- Affiliations
- University of Washington (US)
- Fred Hutch Cancer Center (US)
- Corresponding author
- Tapscott, Stephen J
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2004-05
- Volume
- 14
- Issue
- 4
- Pages
- 465-477
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1970461933
- Cited by
- 332
- References
- 2
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 15 · 2021: 11 · 2020: 10 · 2019: 16 · 2018: 20 · 2017: 14 · 2016: 11 · 2015: 9 · 2014: 14 · 2013: 22 · 2012: 18
- FWCI
- 7.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3364 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (T32CA009657)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR045113, AR045113)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- MyoD, PBX, homeodomain transcription factor, skeletal muscle differentiation, chromatin remodeling, transcriptional activation, inactive chromatin, gene targeting
- MeSH terms
- Pre-B-Cell Leukemia Transcription Factor 1, Animals, Base Sequence, Binding Sites, Cell Differentiation, Genetic Markers, Molecular Sequence Data, Promoter Regions, Genetic, Transcription Factors, Transcriptional Activation, Protein Structure, Tertiary, MyoD Protein, Homeodomain Proteins, Muscle, Skeletal, Gene Expression Regulation, Developmental, Cell Lineage, Body Patterning, NIH 3T3 Cells, Chromatin Assembly and Disassembly, Macromolecular Substances, Mice
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