Dynamic changes in P300 enhancers and enhancer-promoter contacts control mouse cardiomyocyte maturation.

Developmental cell 2023 May 22

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Cardiomyocyte differentiation continues throughout murine gestation and into the postnatal period, driven by temporally regulated expression changes in the transcriptome. The mechanisms that regulate these developmental changes remain incompletely defined. Here, we used cardiomyocyte-specific ChIP-seq of the activate enhancer marker P300 to identify 54,920 cardiomyocyte enhancers at seven stages of murine heart development. These data were matched to cardiomyocyte gene expression profiles at the same stages and to Hi-C and H3K27ac HiChIP chromatin conformation data at fetal, neonatal, and adult stages. Regions with dynamic P300 occupancy exhibited developmentally regulated enhancer activity, as measured by massively parallel reporter assays in cardiomyocytes in vivo, and identified key transcription factor-binding motifs. These dynamic enhancers interacted with temporal changes of the 3D genome architecture to specify developmentally regulated cardiomyocyte gene expressions. Our work provides a 3D genome-mediated enhancer activity landscape of murine cardiomyocyte development. Copyright © 2023 Elsevier Inc. All rights reserved.

Citation

Pingzhu Zhou, Nathan J VanDusen, Yanchun Zhang, Yangpo Cao, Isha Sethi, Rong Hu, Shuo Zhang, Guangyu Wang, Lincai Ye, Neil Mazumdar, Jian Chen, Xiaoran Zhang, Yuxuan Guo, Bin Li, Qing Ma, Julianna Y Lee, Weiliang Gu, Guo-Cheng Yuan, Bing Ren, Kaifu Chen, William T Pu. Dynamic changes in P300 enhancers and enhancer-promoter contacts control mouse cardiomyocyte maturation. Developmental cell. 2023 May 22;58(10):898-914.e7