Transcriptional Control of Subcutaneous Adipose Tissue by the Transcription Factor CTCF Modulates Heterogeneity in Fat Distribution in Women
Edina Erdos,
Katalin Sandor,
Crystal L. Young-Erdos,
Laszlo Halasz,
Steven R. Smith,
Timothy F. Osborne,
Adeline Divoux
Affiliations
Edina Erdos
Division of Diabetes Endocrinology and Metabolism, Departments of Medicine, Biological Chemistry and Pediatrics, Johns Hopkins University School of Medicine, Institute for Fundamental Biomedical Research, Johns Hopkins All Children’s Hospital, St. Petersburg, FL 33701, USA
Katalin Sandor
Division of Diabetes Endocrinology and Metabolism, Departments of Medicine, Biological Chemistry and Pediatrics, Johns Hopkins University School of Medicine, Institute for Fundamental Biomedical Research, Johns Hopkins All Children’s Hospital, St. Petersburg, FL 33701, USA
Crystal L. Young-Erdos
Department of Chemistry & Biochemistry, Eckerd College, St. Petersburg, FL 33711, USA
Laszlo Halasz
Division of Diabetes Endocrinology and Metabolism, Departments of Medicine, Biological Chemistry and Pediatrics, Johns Hopkins University School of Medicine, Institute for Fundamental Biomedical Research, Johns Hopkins All Children’s Hospital, St. Petersburg, FL 33701, USA
Steven R. Smith
Translational Research Institute, Adventhealth, Orlando, FL 32804, USA
Timothy F. Osborne
Division of Diabetes Endocrinology and Metabolism, Departments of Medicine, Biological Chemistry and Pediatrics, Johns Hopkins University School of Medicine, Institute for Fundamental Biomedical Research, Johns Hopkins All Children’s Hospital, St. Petersburg, FL 33701, USA
Adeline Divoux
Translational Research Institute, Adventhealth, Orlando, FL 32804, USA
Determining the mechanism driving body fat distribution will provide insights into obesity-related health risks. We used functional genomics tools to profile the epigenomic landscape to help infer the differential transcriptional potential of apple- and pear-shaped women’s subcutaneous adipose-derived stem cells (ADSCs). We found that CCCTC-binding factor (CTCF) expression and its chromatin binding were increased in ADSCs from pear donors compared to those from apple donors. Interestingly, the pear enriched CTCF binding sites were located predominantly at the active transcription start sites (TSSs) of genes with active histone marks and YY1 motifs and were also associated with pear enriched RNAPII binding. In contrast, apple enriched CTCF binding sites were mainly found at intergenic regions and when identified at TSS, they were enriched with the bivalent chromatin signatures. Altogether, we provide evidence that CTCF plays an important role in differential regulation of subcutaneous ADSCs gene expression and may influence the development of apple vs. pear body shape.
