title: Dynamic GATA4 enhancers shape the chromatin landscape central to heart development and disease.
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.
authors.affiliation: 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.
authors.forename: Aibin
authors.initials: A
authors.lastname: He
authors.affiliation: Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Gu
authors.affiliation: Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Lillian Yi
authors.initials: LY
authors.lastname: Ye
authors.affiliation: Genomics Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Akiyama
authors.affiliation: 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.
authors.forename: Axel
authors.initials: A
authors.lastname: Visel
authors.affiliation: 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.
authors.forename: Len A
authors.initials: LA
authors.lastname: Pennacchio
authors.affiliation: 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.
authors.forename: William T
authors.initials: WT
authors.lastname: Pu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic / Q000235:genetics; D050991:GATA4 Transcription Factor / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006321:Heart / Q000196:embryology*; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000378:metabolism; D008156:Luciferases; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D002843:Chromatin; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D006657:Histones; D008156:Luciferases