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Cited by 200Genomics and Chromatin DynamicsMuscle Physiology and DisordersDevelopmental Biology and Gene Regulation

Snail regulates MyoD binding-site occupancy to direct enhancer switching and differentiation-specific transcription in myogenesis

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Soleimani, Vahab D., Yin, Hang, Jahani-Asl, Arezu, Ming, Hong, Kockx, Christel E.M., van Ijcken, Wilfred F.J., Grosveld, Frank, Rudnicki, Michael A.·2012·Molecular Cell
DOI 10.1016/j.molcel.2012.05.046PMC PMC4580277
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Abstract

In skeletal myogenesis, the transcription factor MyoD activates distinct transcriptional programs in progenitors compared to terminally differentiated cells. Using ChIP-Seq and gene expression analyses, we show that in primary myoblasts, Snail-HDAC1/2 repressive complex binds and excludes MyoD from its targets. Notably, Snail binds E box motifs that are G/C rich in their central dinucleotides, and such sites are almost exclusively associated with genes expressed during differentiation. By contrast, Snail does not bind the A/T-rich E boxes associated with MyoD targets in myoblasts. Thus, Snai1-HDAC1/2 prevent MyoD occupancy on differentiation-specific regulatory elements, and the change from Snail to MyoD binding often results in enhancer switching during differentiation. Furthermore, we show that a regulatory network involving myogenic regulatory factors (MRFs), Snai1/2, miR-30a, and miR-206 acts as a molecular switch that controls entry into myogenic differentiation. Together, these results reveal a regulatory paradigm that directs distinct gene expression programs in progenitors versus terminally differentiated cells.

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Authors
Soleimani, V. D., Yin, H., Jahani-Asl, A., Ming, H., Kockx, C. E. M., van Ijcken, W. F. J., Grosveld, F., & Rudnicki, M. A.
Affiliations
  • University of Ottawa (CA)
  • Erasmus MC (NL)
Corresponding author
Rudnicki, Michael A.
ORCID
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2012-08
Volume
47
Issue
3
Pages
457-468
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2012.05.046
PMC
PMC4580277
OpenAlex
W2045273788
Cited by
200
References
5
Citations by year
2026: 8 · 2025: 7 · 2024: 12 · 2023: 10 · 2022: 20 · 2021: 11 · 2020: 29 · 2019: 14 · 2018: 11 · 2017: 13 · 2016: 19 · 2015: 10 · 2014: 19 · 2013: 13 · 2012: 4
FWCI
5.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Funders
  • Canadian Institutes of Health Research (MOP12080)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR044031)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
snails, MyoD, myogenesis, skeletal muscle differentiation, E-box binding, HDAC1/2, transcriptional repression, myogenic regulatory factors, miR-30a, miR-206, myoblasts, chromatin binding sites
MeSH terms
Snail Family Transcription Factors, Animals, Base Sequence, Cell Differentiation, Enhancer Elements, Genetic, Molecular Sequence Data, Protein Binding, Transcription Factors, Transcription, Genetic, MyoD Protein, Muscle Development, Myoblasts, Skeletal, Mice, Primary Cell Culture

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