The transcription factor nuclear factor I-A (NFIA) is a regulator of brown adipocyte differentiation. Here we show that the most C-terminal 17 amino acid residues of NFIA (which we named pro#3 domain) is required for transcriptional activity of NFIA. Full-length NFIA, but not deletion mutant lacking pro#3 domain rescued impaired Pparg expression and adipogenesis in NFIA-knockout cells. Mechanistically, the ability of NFIA to increase chromatin accessibility is mediated through pro#3 domain. However, the deletion mutant still binds to Myod1 enhancer to decrease chromatin accessibility and represses Myod1 as well as proximally transcribed non-coding RNA called DRReRNA, leading to suppression of myogenic gene program. Therefore, the negative effect of NFIA on myogenic gene program is, at least in part, independent from the positive effect on Pparg expression and its downstream adipogenic gene program. These results uncover multiple ways of action of NFIA to ensure optimal regulation of brown adipocyte differentiation. SOURCE: Hironori Waki (hwaki-tky@umin.ac.jp) -  The University of Tokyo

Pluto Bioinformatics

GSE130389: NFIA differentially controls adipogenic andmyogenic gene program through distinct pathways to ensure adipocyte differentiation [RNA-seq]