Fig. 7.

Schematic summary of this study. (A) In contractile VSMCs, NEAT1 is expressed at a low level, freeing the histone modifier WDR5 to trimethylate histone H3K4 at the promoters of genes encoding SM contractile proteins, thereby opening the chromatin at these loci, facilitating SRF binding and transcriptional activation. WDR5 may possibly function through other cofactors to modulate SM contractile gene expression, as indicated by a question mark. (B) In contrast, in response to vascular injury or mitogens such as PDGF-BB, the increased expression of lncRNA NEAT1 sequestrates WDR5 from MLL complexes at the promoters of genes encoding SM-specific contractile proteins, initiating an epigenetic off state and consequently impairing SRF accessibility to the CArG boxes, resulting in down-regulation of SM-specific gene expression.