Cross species comparison of C/EBP? and PPAR? profiles in mouse and human adipocytes reveals interdependent retention of binding sites.

ABSTRACT: The transcription factors peroxisome proliferator activated receptor ? (PPAR?) and CCAAT/enhancer binding protein ? (C/EBP?) are key transcriptional regulators of adipocyte differentiation and function. We and others have previously shown that binding sites of these two transcription factors show a high degree of overlap and are associated with the majority of genes upregulated during differentiation of murine 3T3-L1 adipocytes.Here we have mapped all binding sites of C/EBP? and PPAR? in human SGBS adipocytes and compared these with the genome-wide profiles from mouse adipocytes to systematically investigate what biological features correlate with retention of sites in orthologous regions between mouse and human. Despite a limited interspecies retention of binding sites, several biological features make sites more likely to be retained. First, co-binding of PPAR? and C/EBP? in mouse is the most powerful predictor of retention of the corresponding binding sites in human. Second, vicinity to genes highly upregulated during adipogenesis significantly increases retention. Third, the presence of C/EBP? consensus sites correlate with retention of both factors, indicating that C/EBP? facilitates recruitment of PPAR?. Fourth, retention correlates with overall sequence conservation within the binding regions independent of C/EBP? and PPAR? sequence patterns, indicating that other transcription factors work cooperatively with these two key transcription factors.This study provides a comprehensive and systematic analysis of what biological features impact on retention of binding sites between human and mouse. Specifically, we show that the binding of C/EBP? and PPAR? in adipocytes have evolved in a highly interdependent manner, indicating a significant cooperativity between these two transcription factors.

SUBMITTER: Schmidt SF 

PROVIDER: S-EPMC3068983 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature