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PreprintCC BYbioRxiv

Transcription-Coupled Chromatin Reinforcement Maintains the Mature Cardiomyocyte State

  1. 1Academia Sinica

Abstract

Chromatin homeostasis is fundamental to maintaining transcriptional programs that stabilize cell states while permitting plasticity for timely state transitions. However, mechanisms that actively sustain mature cell states after their establishment remain poorly defined despite being essential for lifelong maintenance of specialized cellular functions. Here we demonstrate that the transcription-coupled chromatin regulator RNF20 is crucial for maintaining chromatin accessibility at identity-associated promoters that support mature cardiomyocyte transcriptional programs in adult murine cardiomyocytes. Depletion of RNF20 progressively erodes the transcriptional, structural, and functional integrity of adult cardiomyocytes and activates AP-1-associated stress-responsive enhancer elements without cell-cycle re-entry. Spatial transcriptomics further revealed a subendocardial localization of this stress-responsive state. Together, these findings support a model in which transcription-coupled chromatin reinforcement continuously stabilizes the mature cardiomyocyte attractor state while constraining transitions toward pathological cell states.

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BibTeX
@misc{tang2026transcriptioncoupled,
  title = {{Transcription-Coupled Chromatin Reinforcement Maintains the Mature Cardiomyocyte State}},
  author = {H.-H. Tang and H.-Y. Tseng and C.-Y. Lin and C.-F. Kao},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.04.749300},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.04.749300v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Transcription-Coupled Chromatin Reinforcement Maintains the Mature Cardiomyocyte State
AU  - H.-H. Tang
AU  - H.-Y. Tseng
AU  - C.-Y. Lin
AU  - C.-F. Kao
PY  - 2026
DA  - 2026/09/04
PB  - bioRxiv
DO  - 10.64898/2026.09.04.749300
UR  - https://www.biorxiv.org/content/10.64898/2026.09.04.749300v1
AB  - Chromatin homeostasis is fundamental to maintaining transcriptional programs that stabilize cell states while permitting plasticity for timely state transitions. However, mechanisms that actively sustain mature cell states after their establishment remain poorly defined despite being essential for lifelong maintenance of specialized cellular functions. Here we demonstrate that the transcription-coupled chromatin regulator RNF20 is crucial for maintaining chromatin accessibility at identity-associated promoters that support mature cardiomyocyte transcriptional programs in adult murine cardiomyocytes. Depletion of RNF20 progressively erodes the transcriptional, structural, and functional integrity of adult cardiomyocytes and activates AP-1-associated stress-responsive enhancer elements without cell-cycle re-entry. Spatial transcriptomics further revealed a subendocardial localization of this stress-responsive state. Together, these findings support a model in which transcription-coupled chromatin reinforcement continuously stabilizes the mature cardiomyocyte attractor state while constraining transitions toward pathological cell states.
ER  -