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 and William T. Pu ()
Additional contact information
Brynn N. Akerberg: Boston Children’s Hospital
Fei Gu: Boston Children’s Hospital
Nathan J. VanDusen: Boston Children’s Hospital
Xiaoran Zhang: Boston Children’s Hospital
Rui Dong: Dana-Farber Cancer Institute
Kai Li: Boston Children’s Hospital
Bing Zhang: Shanghai Jiao Tong University
Bin Zhou: Shanghai Institutes for Biological Sciences
Isha Sethi: Boston Children’s Hospital
Qing Ma: Boston Children’s Hospital
Lauren Wasson: University of North Carolina at Chapel Hill
Tong Wen: The First Affiliated Hospital of Nanchang University
Jinhua Liu: The First Affiliated Hospital of Nanchang University
Kunzhe Dong: Augusta University
Frank L. Conlon: University of North Carolina at Chapel Hill
Jiliang Zhou: Augusta University
Guo-Cheng Yuan: Dana-Farber Cancer Institute
Pingzhu Zhou: Boston Children’s Hospital
William T. Pu: Boston Children’s Hospital

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12812-3

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