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Cited by 47Genomics and Chromatin DynamicsDevelopmental Biology and Gene RegulationChromatin Remodeling and Cancer

Pax3 cooperates with Ldb1 to direct local chromosome architecture during myogenic lineage specification

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Magli, Alessandro, Baik, June, Pota, Pruthvi, Cordero, Carolina Ortiz, Kwak, Il-Youp, Garry, Daniel J., Love, Paul E., Dynlacht, Brian D. +1 more·2019·Nature Communications
DOI 10.1038/s41467-019-10318-6PMC PMC6534668
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Abstract

Chromatin looping allows enhancer-bound regulatory factors to influence transcription. Large domains, referred to as topologically associated domains, participate in genome organization. However, the mechanisms underlining interactions within these domains, which control gene expression, are not fully understood. Here we report that activation of embryonic myogenesis is associated with establishment of long-range chromatin interactions centered on Pax3-bound loci. Using mass spectrometry and genomic studies, we identify the ubiquitously expressed LIM-domain binding protein 1 (Ldb1) as the mediator of looping interactions at a subset of Pax3 binding sites. Ldb1 is recruited to Pax3-bound elements independently of CTCF-Cohesin, and is necessary for efficient deposition of H3K4me1 at these sites and chromatin looping. When Ldb1 is deleted in Pax3-expressing cells in vivo, specification of migratory myogenic progenitors is severely impaired. These results highlight Ldb1 requirement for Pax3 myogenic activity and demonstrate how transcription factors can promote formation of sub-topologically associated domain interactions involved in lineage specification.

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  • Ectopic tethering of LDB1 to chromatin is sufficient for loop formation, increased deposition of the enhancer mark H3K4me1 and transcriptional activation.

    “Ectopic tethering of LDB1 to chromatin is sufficient for loop formation, increased deposition of the enhancer mark H3K4me1 and transcriptional activation [372, 374].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [372]

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Authors
Magli, A., Baik, J., Pota, P., Cordero, C. O., Kwak, I.-Y., Garry, D. J., Love, P. E., Dynlacht, B. D., & Perlingeiro, R. C. R.
Affiliations
  • University of Minnesota (US)
  • National Institutes of Health (US)
  • New York University (US)
Corresponding author
  • Magli, Alessandro
  • Perlingeiro, Rita C. R.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-05-24
Volume
10
Issue
1
Pages
2316-2316
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-10318-6
PMC
PMC6534668
OpenAlex
W2944878546
Cited by
47
References
11
Citations by year
2026: 5 · 2025: 6 · 2024: 10 · 2023: 4 · 2022: 9 · 2021: 8 · 2020: 5
FWCI
1.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (HL100407R01)
  • U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (GM122395)
  • U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR068786, AR055299, AR071439)
Topics
  • 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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
Pax3, LDB1, chromatin looping, topologically associating domains, embryonic myogenesis, H3K4me1, enhancer-promoter interactions, myogenic progenitor cells, transcriptional regulation
MeSH terms
Mouse Embryonic Stem Cells, PAX3 Transcription Factor, Animals, Cell Differentiation, Cell Line, Chromatin, DNA-Binding Proteins, Embryo, Mammalian, Female, Fibroblasts, Histones, Humans, Male, Mice, Transgenic, Gene Expression Regulation, Developmental, Gene Expression Profiling, Muscle Development, Chromosomes, Mammalian, Mice, Gene Knockdown Techniques, HEK293 Cells, LIM Domain Proteins

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