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

Alessandro Magli, June Baik, Pruthvi Pota, Carolina Ortiz Cordero, Il Youp Kwak, Daniel J Garry, Paul E. Love, Brian D. Dynlacht, Rita Perlingeiro

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number2316
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

LIM Domain Proteins
chromosomes
Chromosomes
specifications
Carrier Proteins
Chromatin
proteins
Specifications
chromatin
Muscle Development
Transcription
Gene expression
Mass spectrometry
Mass Spectrometry
interactions
Transcription Factors
Genes
Chemical activation
Binding Sites
Genome

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

Pax3 cooperates with Ldb1 to direct local chromosome architecture during myogenic lineage specification. / Magli, Alessandro; Baik, June; Pota, Pruthvi; Cordero, Carolina Ortiz; Kwak, Il Youp; Garry, Daniel J; Love, Paul E.; Dynlacht, Brian D.; Perlingeiro, Rita.

In: Nature communications, Vol. 10, No. 1, 2316, 01.12.2019.

Research output: Contribution to journalArticle

Magli, Alessandro ; Baik, June ; Pota, Pruthvi ; Cordero, Carolina Ortiz ; Kwak, Il Youp ; Garry, Daniel J ; Love, Paul E. ; Dynlacht, Brian D. ; Perlingeiro, Rita. / Pax3 cooperates with Ldb1 to direct local chromosome architecture during myogenic lineage specification. In: Nature communications. 2019 ; Vol. 10, No. 1.
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