Abstract
We previously showed that some adipogenic transcription factors such as CEBPB and PPARG directly and indirectly regulate autophagy gene expression in adipogenesis. The order and effect of these events are undetermined. In this study, we modeled the gene expression, DNA-binding of transcriptional regulators, and histone modifications during adipocyte differentiation and evaluated the effect of the regulators on gene expression in terms of direction and magnitude. Then, we identified the overlap of the transcription factors and co-factors binding sites and targets. Finally, we built a chromatin state model based on the histone marks and studied their relation to the factors' binding. Adipogenic factors differentially regulated autophagy genes as part of the differentiation program. Co-regulators associated with specific transcription factors and preceded them to the regulatory regions. Transcription factors differed in the binding time and location, and their effect on expression was either localized or long-lasting. Adipogenic factors disproportionately targeted genes coding for autophagy-specific transcription factors. In sum, a hierarchical arrangement between adipogenic transcription factors and co-factors drives the regulation of autophagy during adipocyte differentiation.
Highlights
Previous studies suggested one-to-one interactions between adipogenic transcription factors and autophagy
We found that pre-adipocytes responded to MDI induction by changes in gene expression as early as 4 hours and continued for days
The size of the response was reasonably stable during the differentiation and was evenly split (25% at a false-discovery rate (FDR) < 0.2) between genes regulated in either direction
Summary
Previous studies suggested one-to-one interactions between adipogenic transcription factors and autophagy. FOXO1, a transcription factor with several autophagy targets, was suggested to the repress Pparg gene in the presence of insulin sensitizers [2]. This repression is likely to be lifted in early adipogenesis. A previous study from our laboratory showed that autophagy gene products are regulated as part of the transcription program of adipogenesis [3]. This regulation is achieved through adipogenic transcription factors PPARG and CEBPB either directly or indirectly through autophagy specific factors.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
