A reference map of murine cardiac transcription factor chromatin occupancy identifies dynamic and conserved enhancers

Brynn N. Akerberg, Fei Gu, Nathan J. VanDusen, Xiaoran Zhang, Rui Dong, Kai Li, Bing Zhang, Bin Zhou, Isha Sethi, Qing Ma, Lauren Wasson, Tong Wen, Jinhua Liu, Kunzhe Dong, Frank L. Conlon, Jiliang Zhou, Guo Cheng Yuan, Pingzhu Zhou, William T. Pu

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Mapping the chromatin occupancy of transcription factors (TFs) is a key step in deciphering developmental transcriptional programs. Here we use biotinylated knockin alleles of seven key cardiac TFs (GATA4, NKX2-5, MEF2A, MEF2C, SRF, TBX5, TEAD1) to sensitively and reproducibly map their genome-wide occupancy in the fetal and adult mouse heart. These maps show that TF occupancy is dynamic between developmental stages and that multiple TFs often collaboratively occupy the same chromatin region through indirect cooperativity. Multi-TF regions exhibit features of functional regulatory elements, including evolutionary conservation, chromatin accessibility, and activity in transcriptional enhancer assays. H3K27ac, a feature of many enhancers, incompletely overlaps multi-TF regions, and multi-TF regions lacking H3K27ac retain conservation and enhancer activity. TEAD1 is a core component of the cardiac transcriptional network, co-occupying cardiac regulatory regions and controlling cardiomyocyte-specific gene functions. Our study provides a resource for deciphering the cardiac transcriptional regulatory network and gaining insights into the molecular mechanisms governing heart development.

Original languageEnglish (US)
Article number4907
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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