Transcriptional regulation by the orphan nuclear receptor NR5A2 links cell differentiation with inflammation in the pancreas
Speaker: Francisco Real, MD, Ph.D.
Epithelial Carcinogenesis Group, Centro Nacional de Investigaciones Oncológicas (CNIO) Madrid (Spain)
Organizers: IRB Barcelona
Date: Friday January 2017 12:00h
Place: Fèlix Serratosa, Parc Científic de Barcelona, Spain
Host: Dr.Eduard Batlle, IRB Barcelona
It is thought that tissue-specific differentiation and inflammatory programs independently contribute to cancer. Using a combination of murine and human data, we show that the orphan nuclear receptor NR5A2 is not only a key regulator of pancreas differentiation but also a major regulator of inflammatory programs. Upon genetic and pharmacological perturbation, Nr5a2 undergoes a dramatic transcriptional switch relocating from tissue-specific to inflammatory loci in an AP-1-dependent manner. These findings provide compelling evidence that the same transcriptional networks supporting homeostasis can be subverted to foster inflammation upon genetic or environmental constraints.