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

Aibin He (), Fei Gu, Yong Hu, Qing Ma, Lillian Yi Ye, Jennifer A. Akiyama, Axel Visel, Len A. Pennacchio and William T. Pu ()
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Aibin He: Boston Children’s Hospital, 300 Longwood Avenue
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
Len A. Pennacchio: Lawrence Berkeley National Laboratory, 1 Cyclotron Road
William T. Pu: Boston Children’s Hospital, 300 Longwood Avenue

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5907

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