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Dynamic and Coordinated Epigenetic Regulation of Developmental Transitions in the Cardiac Lineage

Author(s)
Wamstad, Joseph A.; Alexander, Jeffrey M.; Truty, Rebecca M.; Shrikumar, Avanti; Li, Fugen; Eilertson, Kirsten E.; Ding, Huiming; Wylie, John N.; Pico, Alexander R.; Capra, John A.; Erwin, Genevieve; Kattman, Steven J.; Keller, Gordon M.; Srivastava, Deepak; Levine, Stuart S.; Pollard, Katherine S.; Holloway, Alisha K.; Boyer, Laurie; Bruneau, Benoit G.; ... Show more Show less
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Abstract
Heart development is exquisitely sensitive to the precise temporal regulation of thousands of genes that govern developmental decisions during differentiation. However, we currently lack a detailed understanding of how chromatin and gene expression patterns are coordinated during developmental transitions in the cardiac lineage. Here, we interrogated the transcriptome and several histone modifications across the genome during defined stages of cardiac differentiation. We find distinct chromatin patterns that are coordinated with stage-specific expression of functionally related genes, including many human disease-associated genes. Moreover, we discover a novel preactivation chromatin pattern at the promoters of genes associated with heart development and cardiac function. We further identify stage-specific distal enhancer elements and find enriched DNA binding motifs within these regions that predict sets of transcription factors that orchestrate cardiac differentiation. Together, these findings form a basis for understanding developmentally regulated chromatin transitions during lineage commitment and the molecular etiology of congenital heart disease.
Date issued
2012-09
URI
http://hdl.handle.net/1721.1/83607
Department
Massachusetts Institute of Technology. Department of Biology
Journal
Cell
Publisher
Elsevier B.V.
Citation
Wamstad, Joseph A., Jeffrey M. Alexander, Rebecca M. Truty, Avanti Shrikumar, Fugen Li, Kirsten E. Eilertson, Huiming Ding, et al. “Dynamic and Coordinated Epigenetic Regulation of Developmental Transitions in the Cardiac Lineage.” Cell 151, no. 1 (September 2012): 206-220.© 2012 Elsevier Inc.
Version: Final published version
ISSN
00928674
1097-4172

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