Tbx5 maintains atrial identity in postnatal cardiomyocytes by regulating an atrial-specific enhancer network

Mason E.,Sweat1; Yangpo,Cao1,2; Xiaoran,Zhang1; Ozanna,Burnicka-Turek3; Carlos,Perez-Cervantes3; Arulsamy,Kulandaisamy1; Fujian,Lu1; Erin M.,Keating1; Brynn N.,Akerberg1; Qing,Ma1; Hiroko,Wakimoto4; Joshua M.,Gorham4; Lauren D.,Hill1; Mi Kyoung,Song1,5; Michael A.,Trembley1; Peizhe,Wang1; Matteo,Gianeselli1; Maksymilian,Prondzynski1; Raul H.,Bortolin1; Vassilios J.,Bezzerides1; Kaifu,Chen1; Jonathan G.,Seidman4; Christine E.,Seidman4; Ivan P.,Moskowitz3; William T.,Pu1

2023-10-12

10.1038/s44161-023-00334-7

Cardiovascular Research   影响因子和分区

2731-0590

2731-0590

["Understanding how the atrial and ventricular heart chambers maintain distinct identities is a prerequisite for treating chamber-specific diseases. In this study, we selectively knocked out the transcription factor Tbx5 in the atrial working myocardium to evaluate its requirement for atrial identity. Atrial Tbx5 inactivation downregulated atrial cardiomyocyte (aCM)-selective gene expression. Using concurrent single-nucleus transcriptome and open chromatin profiling, genomic accessibility differences were identified between control and Tbx5 knockout aCMs, revealing that 69% of the control-enriched ATAC regions were bound by TBX5. Genes associated with these regions were downregulated in knockout aCMs, suggesting that they function as TBX5-dependent enhancers. Comparing enhancer chromatin looping using H3K27ac HiChIP identified 510 chromatin loops sensitive to TBX5 dosage, and 74.8% of control-enriched loops contained anchors in control-enriched ATAC regions. Together, these data demonstrate that TBX5 maintains the atrial gene expression program by binding to and preserving the tissue-specific chromatin architecture of atrial enhancers.","Sweat, Cao et al. used different genetic and epigenetic approaches to show that Tbx5 is essential for the maintenance of atrial identity in postnatal cardiomyocytes by binding atrial-specific enhancers and maintaining the atrial-specific chromatin architecture, in a dose-dependent manner."]

SCI ; ESCI

英语

共同第一 ; 其他

U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)["T32HL007572","F32 F32HL163877","R01HL156503"]

Cardiovascular System & Cardiology

Cardiac & Cardiovascular Systems

WOS:001125047300007

Springer Science and Business Media LLC

CLINICAL MEDICINE

人工提交

1.Department of Cardiology, Boston Children’s Hospital, Boston, MA, USA
2.Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, China
3.Department of Pediatrics, Pathology, and Human Genetics, University of Chicago, Chicago, IL, USA
4.Department of Genetics, Harvard Medical School, Boston, MA, USA
5.Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea

Mason E.,Sweat,Yangpo,Cao,Xiaoran,Zhang,et al. Tbx5 maintains atrial identity in postnatal cardiomyocytes by regulating an atrial-specific enhancer network[J]. Cardiovascular Research,2023,2(10):881-898.

Mason E.,Sweat.,Yangpo,Cao.,Xiaoran,Zhang.,Ozanna,Burnicka-Turek.,Carlos,Perez-Cervantes.,...&William T.,Pu.(2023).Tbx5 maintains atrial identity in postnatal cardiomyocytes by regulating an atrial-specific enhancer network.Cardiovascular Research,2(10),881-898.

Mason E.,Sweat,et al."Tbx5 maintains atrial identity in postnatal cardiomyocytes by regulating an atrial-specific enhancer network".Cardiovascular Research 2.10(2023):881-898.