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Dynamic GATA4 enhancers shape the chromatin landscape central to heart development and disease

Author

Listed:
  • Aibin He

    (Boston Children’s Hospital, 300 Longwood Avenue
    Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University)

  • Fei Gu

    (Boston Children’s Hospital, 300 Longwood Avenue)

  • Yong Hu

    (Boston Children’s Hospital, 300 Longwood Avenue)

  • Qing Ma

    (Boston Children’s Hospital, 300 Longwood Avenue)

  • Lillian Yi Ye

    (Boston Children’s Hospital, 300 Longwood Avenue)

  • Jennifer A. Akiyama

    (Lawrence Berkeley National Laboratory, 1 Cyclotron Road)

  • Axel Visel

    (Lawrence Berkeley National Laboratory, 1 Cyclotron Road
    2800 Mitchell Drive
    School of Natural Sciences, University of California, 5200 North Lake Rd)

  • Len A. Pennacchio

    (Lawrence Berkeley National Laboratory, 1 Cyclotron Road
    2800 Mitchell Drive)

  • William T. Pu

    (Boston Children’s Hospital, 300 Longwood Avenue
    Harvard Stem Cell Institute, Harvard University, 1350 Massachusetts Avenue, Suite 727W)

Abstract

How stage-specific enhancer dynamics modulate gene expression patterns essential for organ development, homeostasis and disease is not well understood. Here, we addressed this question by mapping chromatin occupancy of GATA4—a master cardiac transcription factor—in heart development and disease. We find that GATA4 binds and participates in establishing active chromatin regions by stimulating H3K27ac deposition, which facilitates GATA4-driven gene expression. GATA4 chromatin occupancy changes markedly between fetal and adult heart, with a limited binding sites overlap. Cardiac stress restored GATA4 occupancy to a subset of fetal sites, but many stress-associated GATA4 binding sites localized to loci not occupied by GATA4 during normal heart development. Collectively, our data show that dynamic, context-specific transcription factors occupancy underlies stage-specific events in development, homeostasis and disease.

Suggested Citation

  • Aibin He & Fei Gu & Yong Hu & Qing Ma & Lillian Yi Ye & Jennifer A. Akiyama & Axel Visel & Len A. Pennacchio & William T. Pu, 2014. "Dynamic GATA4 enhancers shape the chromatin landscape central to heart development and disease," Nature Communications, Nature, vol. 5(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5907
    DOI: 10.1038/ncomms5907
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    Cited by:

    1. Samuel Abassah-Oppong & Matteo Zoia & Brandon J. Mannion & Raquel Rouco & Virginie Tissières & Cailyn H. Spurrell & Virginia Roland & Fabrice Darbellay & Anja Itum & Julie Gamart & Tabitha A. Festa-Da, 2024. "A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival," Nature Communications, Nature, vol. 15(1), pages 1-24, December.

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