Comparative Epigenomic Analysis of Murine and Human Adipogenesis

SummaryWe 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.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (349 K)Download as PowerPoint slideHighlights► Chromatin state maps were generated throughout murine and human adipogenesis ► Most active cis-regulatory elements differ between species ► Many differences are due to evolutionary turnover of transcription factor motifs ► Motif enrichment predicted that PLZF and SRF play a repressive role in adipogenesis