Decisions, decisions ... SRF coactivators and smooth muscle myogenesis

Accessory cofactors for SRF play key roles in signalresponsive control of CArG-dependent transcription. Myocardin is expressed in developing and adult vascular SMCs, physically associates with SRF, and greatly potentiates SRF-dependent transcription of multiple SMC marker genes. While it is tempting to speculate that myocardin will turn out to be a key factor in control of vascular SMC differentiation in vivo, it is unlikely to account for the full range of SMC differentiation phenotypes described in normal and diseased artery wall. In that regard, other SRF cofactors including MRTFs, Nkx, and paired-type homeodomain proteins, GATA factors, HOP, Barx2B, chromatin-organizing factors HMGI(Y) and SSRP1, YY1, and LIM domain-containing proteins including Crp1 and Crp2 are also likely to be involved. It will be of great interest to determine if and to what extent myocardin interacts with one or more of these SRF cofactors, whether or not myocardin is a target for posttranslational modifications by MAP kinase or rho kinase signaling pathways, and how the interplay between SRF-MADS domain-interacting proteins controls the expression of various CArG-dependent genes in the transitions between growth and differentiation characteristic of the vascular SMC in vivo.