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Nat Commun. 2014 Sep 24;5:4907. doi: 10.1038/ncomms5907.

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

Author information

1
1] Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA [2] Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, People's Republic of China.
2
Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
3
Genomics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720, USA.
4
1] Genomics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720, USA [2] United States Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, California 94598, USA [3] School of Natural Sciences, University of California, 5200 North Lake Rd, Merced, California 95343, USA.
5
1] Genomics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720, USA [2] United States Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, California 94598, USA.
6
1] Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA [2] Harvard Stem Cell Institute, Harvard University, 1350 Massachusetts Avenue, Suite 727W, Cambridge, Massachusetts 02138, USA.

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.

PMID:
25249388
PMCID:
PMC4236193
DOI:
10.1038/ncomms5907
[Indexed for MEDLINE]
Free PMC Article

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