Dynamic and coordinated epigenetic regulation of developmental transitions in the cardiac lineage

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 trans...

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Published in:Cell Vol. 151; no. 1; p. 206
Main Authors: 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 A, Bruneau, Benoit G
Format: Journal Article
Language:English
Published: United States 28.09.2012
Subjects:
Animals
Cell Differentiation
Chromatin - metabolism
Embryonic Stem Cells - metabolism
Enhancer Elements, Genetic
Epigenesis, Genetic
Gene Regulatory Networks
Heart - embryology
Humans
Mice
Myocardium - cytology
Transcription Factors - metabolism
Transcriptome
ISSN:1097-4172, 1097-4172
Online Access:Get more information
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Summary: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.
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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2012.07.035