BACH1 deficiency impedes differentiation of vascular smooth muscle cell from hESCs via reducing the CARM1-catalyzed H3R17me2
Vascular smooth muscle cells (VSMCs) derived from human embryonic stem cells (hESCs) have been considered as a potential therapeutic application in vascular diseases. The transcription factor BTB and CNC homology 1 (BACH1) participates in stem cell development and has an increased expression during the VSMCs differentiation process. Knockout of BACH1 inhibits the differentiation of hESCs into VSMCs, whereas overexpression of BACH1 promotes VSMCs differentiation after the mesoderm stage. Mechanistically, BACH1 interacts with Coactivator-associated arginine methyltransferase 1 (CARM1) in a bZIP domain-dependent manner. BACH1 recruits CARM1 and its specific histone mark H3R17me2 to VSMC marker genes promoters, thus up-regulating target gene expression. BACH1-induced promotion of VSMC marker genes was partially abolished by the knockdown of CARM1 or H3R17me2. Thus, our results demonstrate the regulatory role of BACH1 and CARM1 in VSMCs differentiation. Overall design: RNA-Seq + CUT&Tag