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CHD4 Interacts With TBX5 to Maintain the Gene Regulatory Network of Postnatal Atrial Cardiomyocytes

ABSTRACT: CHD4 Interacts With TBX5 to Maintain the Gene Regulatory Network of Postnatal Atrial Cardiomyocytes

PROVIDER: PRJNA1260502 | ENA |

REPOSITORIES: ENA

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CHD4 Interacts With TBX5 to Maintain the Gene Regulatory Network of Postnatal Atrial Cardiomyocytes

Project description:Atrial fibrillation (AF), the most common sustained arrhythmia, affects 59 million individuals worldwide. The transcription factor TBX5 is essential for normal atrial rhythm, and its inactivation causes loss of aCM enhancer accessibility, looping, and transcriptional identity, and causes spontaneous AF. Here we investigated mechanisms by which TBX5 regulates chromatin organization. We found that TBX5 recruits CHD4, a chromatin remodeling ATPase canonically associated with the NuRD repressor complex, to 33,170 genomic regions (TBX5-enhanced CHD4 sites). Combined snRNA-seq and snATAC-seq of CHD4 knockout (KO) and control aCMs revealed that CHD4 has both gene activator and repressor functions. CHD4-repressed genes included sarcomeric proteins from non-CM cell lineages. CHD4-activated genes were characterized by TBX5-enhanced CHD4 recruitment, which enhanced chromatin accessibility and promoted the expression of aCM identity genes. This mechanism of TBX5 recruitment of CHD4 was critical for sinus rhythm because Chd4AKO mice had increased vulnerability to AF. Our findings reveal that CHD4 is essential for maintaining aCM gene expression, aCM identity, and atrial rhythm homeostasis.

2025-08-04 | GSE296675 | GEO

CHD4 Interacts With TBX5 to Maintain the Gene Regulatory Network of Postnatal Atrial Cardiomyocytes [ChIP-seq]

2025-08-04 | GSE284095 | GEO

CHD4 Interacts With TBX5 to Maintain the Gene Regulatory Network of Postnatal Atrial Cardiomyocytes [bulk RNA-seq]

2025-08-04 | GSE284094 | GEO

CHD4 Interacts With TBX5 to Maintain the Gene Regulatory Network [multiome]

2025-08-04 | GSE284093 | GEO

CHD4 Interacts With TBX5 to Maintain the Gene Regulatory Network of Postnatal Atrial Cardiomyocytes [ChIP-seq]

Project description:CHD4 Interacts With TBX5 to Maintain the Gene Regulatory Network of Postnatal Atrial Cardiomyocytes [ChIP-seq]

| PRJNA1196989 | ENA

CHD4 Interacts With TBX5 to Maintain the Gene Regulatory Network of Postnatal Atrial Cardiomyocytes [bulk RNA-seq]

Project description:CHD4 Interacts With TBX5 to Maintain the Gene Regulatory Network of Postnatal Atrial Cardiomyocytes [bulk RNA-seq]

| PRJNA1196991 | ENA

CHD4 Interacts With TBX5 to Maintain the Gene Regulatory Network [multiome]

Project description:CHD4 Interacts With TBX5 to Maintain the Gene Regulatory Network [multiome]

| PRJNA1196990 | ENA

Tbx5 regulatory element controls atrial function and heart size II

Project description:Left atrial RNA-seq of Tbx5(REint), Tbx5(REdown), Tbx5(Reint);Prrx1(RE) and control adult mice

2023-02-10 | GSE189342 | GEO

TBX5 Adult Knockout Left Atrial Gene Expression

Project description:TBX5 removed from adult mice with R26CreERt2, left and right atrial RNA extracted and sequenced.

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Reduced TBX5 dosage causes human atrial disease by undermining developmental gene regulation of atrial cardiomyocyte identity [scRNA-seq]

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