GSE25426
Functional and cellular constraints that shaped the PPARg binding landscape in human and mouse macrophages: human ChIP-Seq
Genome-wide comparisons of transcription factor binding sites in different species allow for a direct evaluation of the evolutionary constraints that shape transcription factor binding landscapes. To gain insights into the evolution of the PPARg-dependent transcriptional network, we obtained binding data for PPARg, RXR and PU.1 in human macrophages and compared the profiles to matching data from mouse macrophages (Lefterova et al. 2010 (PMID 20176806); GSE21314). We found that PPARg binding was highly divergent and only 5% of the PPARg-bound regions were occupied in both species. Despite the low conservation of PPARg binding sites, conserved PPARg target genes contribute more than 30% to the functional target genes identified in human macrophages. In addition, conserved target genes are strongly enriched for lipid metabolic functions. We detected the lineage-specification factor PU.1 at the majority of human PPARg binding sites. This confirmed the juxtaposed binding configuration found in mouse macrophages and demonstrated the preservation of tissue-specific adjacent PPARg-Pu.1 binding in the absence of individual binding site conservation. Finally, based on this PPARg and PU.1 binding between human and mouse, we suggest a mechanism by which PU.1 facilitates PPARg binding site turnover in macrophages. Overall design: Genome-wide location analysis for 3 transcription factors (PPARg, RXR and PU.1) in a human monocytic cell line (THP-1). This submission represents the human binding data component of the study.