Comparative Epigenomic Analysis of Murine and Human Adipogenesis
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Author(s)
Gimble, Jeffrey M.
Mikkelsen, Tarjei
Xu, Zhao
Zhang, Xiaolan
Wang, Li
Lander, Eric Steven
Rosen, Evan D
Date Issued
October 2010
Journal
Cell
Publisher
Elsevier
Citation
Mikkelsen, Tarjei S., Zhao Xu, Xiaolan Zhang, Li Wang, Jeffrey M. Gimble, Eric S. Lander, and Evan D. Rosen. “Comparative Epigenomic Analysis of Murine and Human Adipogenesis.” Cell 143, no. 1 (October 2010): 156–169.
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Author's final manuscript
Abstract
We report the generation and comparative analysis of genome-wide chromatin state maps, PPARγ and CTCF localization maps, and gene expression profiles from murine and human models of adipogenesis. The data provide high-resolution views of chromatin remodeling during cellular differentiation and allow identification of thousands of putative preadipocyte- and adipocyte-specific cis-regulatory elements based on dynamic chromatin signatures. We find that the specific locations of most such elements differ between the two models, including at orthologous loci with similar expression patterns. Based on sequence analysis and reporter assays, we show that these differences are determined, in part, by evolutionary turnover of transcription factor motifs in the genome sequences and that this turnover may be facilitated by the presence of multiple distal regulatory elements at adipogenesis-dependent loci. We also utilize the close relationship between open chromatin marks and transcription factor motifs to identify and validate PLZF and SRF as regulators of adipogenesis.
MIT Department
Institute for Medical Engineering and Science
Broad Institute of MIT and Harvard
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Massachusetts Institute of Technology. Department of Mathematics
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2010.09.006
