Evidence map›Paper›PMID 40799140›Full record

ArticleCirculation2025

TBX5 and CHD4 Coordinately Activate Atrial Cardiomyocyte Genes to Maintain Cardiac Rhythm Homeostasis.

Mason E Sweat, Wei Shi, Yan Y Sweat, Jie Li, Jiajin Li, Erin M Keating, Anna Ponek, Qing Ma, Chaehyoung Park, Michael A Trembley and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Role of CHD chromatin remodelers in heart development.World journal of pediatrics : WJP · 2026
    Review
  5. Review
  6. Review
  7. Enhancer Dynamics for Gene Regulation in the Cardiovascular System.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Mason E Sweat *Department of Cardiology, Boston Children's Hospital, MA (M.E.S., Y.Y.S., Jie Li, Jiajin Li, E.M.K., A.P., Q.M., C.P., M.A.T., Y.W., C.H., V.J.B., W.T.P.).ORCID 0000-0002-5400-1266
Wei Shi *Department of Biology, University of North Carolina at Chapel Hill (W.S., F.L.C.).ORCID 0009-0001-2085-0323
Yan Y SweatDepartment of Cardiology, Boston Children's Hospital, MA (M.E.S., Y.Y.S., Jie Li, Jiajin Li, E.M.K., A.P., Q.M., C.P., M.A.T., Y.W., C.H., V.J.B., W.T.P.).ORCID 0000-0002-9903-8054
Jie LiDepartment of Cardiology, Boston Children's Hospital, MA (M.E.S., Y.Y.S., Jie Li, Jiajin Li, E.M.K., A.P., Q.M., C.P., M.A.T., Y.W., C.H., V.J.B., W.T.P.).
Jiajin LiDepartment of Cardiology, Boston Children's Hospital, MA (M.E.S., Y.Y.S., Jie Li, Jiajin Li, E.M.K., A.P., Q.M., C.P., M.A.T., Y.W., C.H., V.J.B., W.T.P.).
Erin M KeatingDepartment of Cardiology, Boston Children's Hospital, MA (M.E.S., Y.Y.S., Jie Li, Jiajin Li, E.M.K., A.P., Q.M., C.P., M.A.T., Y.W., C.H., V.J.B., W.T.P.).
Anna PonekDepartment of Cardiology, Boston Children's Hospital, MA (M.E.S., Y.Y.S., Jie Li, Jiajin Li, E.M.K., A.P., Q.M., C.P., M.A.T., Y.W., C.H., V.J.B., W.T.P.).ORCID 0009-0008-5366-881X
Qing MaDepartment of Cardiology, Boston Children's Hospital, MA (M.E.S., Y.Y.S., Jie Li, Jiajin Li, E.M.K., A.P., Q.M., C.P., M.A.T., Y.W., C.H., V.J.B., W.T.P.).ORCID 0000-0002-5625-1330
Chaehyoung ParkDepartment of Cardiology, Boston Children's Hospital, MA (M.E.S., Y.Y.S., Jie Li, Jiajin Li, E.M.K., A.P., Q.M., C.P., M.A.T., Y.W., C.H., V.J.B., W.T.P.).
Michael A TrembleyDepartment of Cardiology, Boston Children's Hospital, MA (M.E.S., Y.Y.S., Jie Li, Jiajin Li, E.M.K., A.P., Q.M., C.P., M.A.T., Y.W., C.H., V.J.B., W.T.P.).ORCID 0000-0001-6675-9325
Yi WangDepartment of Cardiology, Boston Children's Hospital, MA (M.E.S., Y.Y.S., Jie Li, Jiajin Li, E.M.K., A.P., Q.M., C.P., M.A.T., Y.W., C.H., V.J.B., W.T.P.).ORCID 0000-0002-0291-5314
Cuilan HouDepartment of Cardiology, Boston Children's Hospital, MA (M.E.S., Y.Y.S., Jie Li, Jiajin Li, E.M.K., A.P., Q.M., C.P., M.A.T., Y.W., C.H., V.J.B., W.T.P.).
Vassilios J BezzeridesDepartment of Cardiology, Boston Children's Hospital, MA (M.E.S., Y.Y.S., Jie Li, Jiajin Li, E.M.K., A.P., Q.M., C.P., M.A.T., Y.W., C.H., V.J.B., W.T.P.).ORCID 0000-0003-0825-6580
Frank L ConlonDepartment of Biology, University of North Carolina at Chapel Hill (W.S., F.L.C.).ORCID 0000-0002-5027-0397
William T PuDepartment of Cardiology, Boston Children's Hospital, MA (M.E.S., Y.Y.S., Jie Li, Jiajin Li, E.M.K., A.P., Q.M., C.P., M.A.T., Y.W., C.H., V.J.B., W.T.P.).ORCID 0000-0002-4551-8079

Funding

Using Patient-Reported Outcomes, Inflammatory Profiles, and Cardiovascular Phenogroups to Expand the Definition of Heart Failure with Preserved Ejection FractionP20GM152326 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Wei Shi · 2024 to 2026
$10.3M
Transcriptional regulation of chamber selective gene expressionR01HL156503 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI William Tswenching Pu · 2021 to 2026
$4.0M
The molecular determinants of atrial fibrillationR00HL173573 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI Mason Eric Sweat · 2025 to 2026
$498k
The molecular determinants of atrial fibrillationK99HL173573 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI SWEAT, MASON ERIC · 2024 to 2025
$246k
NHLBI NIH HHS K99 HL173573NHLBI NIH HHS R00 HL173573NHLBI NIH HHS R01 HL156503NIGMS NIH HHS P20 GM152326
6 · The paper itself

Abstract

backgroundAtrial fibrillation, the most common sustained arrhythmia, affects 59 million individuals worldwide. The transcription factor TBX5 (T-box 5) is essential for normal atrial rhythm. Its inactivation causes loss of atrial cardiomyocyte (aCM) enhancer accessibility, looping, transcriptional identity, and spontaneous atrial fibrillation. TBX5 interacts with CHD4 (chromodomain helicase DNA-binding protein 4), a chromatin remodeling ATPase canonically associated with the NuRD (nucleosome remodeling and deacetylase) repressor complex.

methodsWe investigated mechanisms by which TBX5 regulates chromatin organization by studying mice with aCM-selective inactivation of TBX5 or CHD4. We integrated multiple genomics approaches including concurrent single-nucleus transcriptome and open chromatin profiling and genome-wide TBX5 and CHD4 chromatin occupancy assays.

resultsWe found that TBX5 recruits CHD4 to 33 170 genomic regions (TBX5-enhanced CHD4 sites). In addition to the canonical repressive activity of CHD4, we uncovered a CHD4 activator function predominantly at sites to which it was recruited by TBX5. TBX5-enhanced CHD4 recruitment increased local chromatin accessibility and promoted the expression of aCM identity genes. This mechanism of CHD4 recruitment by TBX5 was crucial for sinus rhythm; mice with CHD4 inactivation in aCMs had increased atrial fibrillation vulnerability. Assaying TBX5 binding in

conclusionsOur findings reveal that normal atrial rhythm requires CHD4, which activates and represses atrial genes in a context-dependent manner to maintain aCM gene expression, aCM identity, and atrial rhythm homeostasis.

Indexed as

Atrial FibrillationHeart AtriaHeart RateMyocytes, CardiacT-Box Domain ProteinsAnimalsHomeostasisHumansMi-2 Nucleosome Remodeling and Deacetylase ComplexMiceMi-2 Nucleosome Remodeling and Deacetylase ComplexT-Box Domain ProteinsT-box transcription factor 5arrhythmias, cardiacatrial fibrillationtranscription factors

Identifiers

PMID40799140
PMCPMC12479101

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.