The landscape of accessible chromatin in quiescent cardiac fibroblasts and cardiac fibroblasts activated after myocardial infarction

Authors

Chaoyang Li, School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA.
Jiangwen Sun, Department of Computer Science, Old Dominion University, Norfolk, VA, USA.
Qianglin Liu, School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA.
Sanjeeva Dodlapati, Department of Computer Science, Old Dominion University, Norfolk, VA, USA.
Hao Ming, School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA.
Leshan Wang, School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA.
Yuxia Li, School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA.
Rui Li, Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
Zongliang Jiang, School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA.
Joseph Francis, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, La, USA.
Xing Fu, School of Animal Sciences, AgCenter, Louisiana State University, Baton Rouge, LA, USA.

Document Type

Article

Publication Date

10-25-2021

Abstract

After myocardial infarction, the massive death of cardiomyocytes leads to cardiac fibroblast proliferation and myofibroblast differentiation, which contributes to the extracellular matrix remodelling of the infarcted myocardium. We recently found that myofibroblasts further differentiate into matrifibrocytes, a newly identified cardiac fibroblast differentiation state. Cardiac fibroblasts of different states have distinct gene expression profiles closely related to their functions. However, the mechanism responsible for the gene expression changes during these activation and differentiation events is still not clear. In this study, the gene expression profiling and genome-wide accessible chromatin mapping of mouse cardiac fibroblasts isolated from the uninjured myocardium and the infarct at multiple time points corresponding to different differentiation states were performed by RNA sequencing (RNA-seq) and the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), respectively. ATAC-seq peaks were highly enriched in the promoter area and the distal area where the enhancers are located. A positive correlation was identified between the expression and promoter accessibility for many dynamically expressed genes, even though evidence showed that mechanisms independent of chromatin accessibility may also contribute to the gene expression changes in cardiac fibroblasts after MI. Moreover, motif enrichment analysis and gene regulatory network construction identified transcription factors that possibly contributed to the differential gene expression between cardiac fibroblasts of different states.

Publication Source (Journal or Book title)

Epigenetics

First Page

1

Last Page

20

Recommended Citation

Li, C., Sun, J., Liu, Q., Dodlapati, S., Ming, H., Wang, L., Li, Y., Li, R., Jiang, Z., Francis, J., & Fu, X. (2021). The landscape of accessible chromatin in quiescent cardiac fibroblasts and cardiac fibroblasts activated after myocardial infarction. Epigenetics, 1-20. https://doi.org/10.1080/15592294.2021.1982158