Dynamic and Coordinated Epigenetic Regulation of Developmental Transitions in the Cardiac Lineage
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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.
Date Issued
September 2012
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.
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Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.cell.2012.07.035