Negative autoregulation of BMP dependent transcription by SIN3B splicing reveals a role for RBM39.

摘要: BMP signalling is negatively autoregulated by several genes including SMAD6, Noggin and Gremlin, autoregulators are possible targets for enhancing in disorders such as fibrosis pulmonary hypertension. To identify novel negative regulators of signalling, we used siRNA screening mouse C2C12 cells with a BMP-responsive luciferase reporter. Knockdown splicing factors increased BMP4-dependent transcription target gene expression. RBM39 produced the greatest enhancement activity. Transcriptome-wide RNA sequencing identified change Sin3b exon usage after knockdown. SIN3B histone deacetylases to chromatin repress transcription. In mouse, produces long short isoforms, isoform lacking ability recruit HDACs. BMP4 induced shift expression isoform, this ratio was prevented enhanced transcription, whereas knockdown did not. We propose that part alternative splicing, plays role process.