A rare human sequence variant reveals myocardin autoinhibition.

ABSTRACT: Myocardin (MYOCD) is a transcriptional co-activator that promotes cardiac or smooth muscle gene programs through its interaction with myocyte-enhancing factor (MEF2) or serum-response factor (SRF). Isoforms of MYOCD with a truncated amino terminus show increased activity when compared with those with the full-length amino terminus, but how this is achieved remains unknown. We identified a rare human sequence variation in MYOCD in a patient with congenital heart disease that resulted in a missense mutation at codon 259 (K259R). This variation created a hypomorphic cardiac isoform with impaired SRF binding and transactivation capacity but did not impair the smooth muscle isoform of MYOCD, which lacks the amino terminus. Consistent with differential effects of the amino terminus on the K259R

SUBMITTER: Ransom JF 

PROVIDER: S-EPMC2602885 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature