Conditional knockout of serum response factor in the heart-forming region blocked the appearance of rhythmic beating myocytes and attenuated myofibril proteins while up-regulating biomineralization genes.
SRF is essential for nascent sarcomerogenesis and represses the biomineralization gene program in the developing heart via microRNA regulation.
Our conditional serum response factor (SRF) knockout, Srf (Cko), in the heart-forming region blocked the appearance of rhythmic beating myocytes, one of the earliest cardiac defects caused by the ablation of a cardiac-enriched transcription factor. The appearance of Hand1 and Smyd1, transcription and chromatin remodeling factors; Acta1, Acta2, Myl3, and Myom1, myofibril proteins; and calcium-activated potassium-channel gene activity (KCNMB1), the channel protein, were powerfully attenuated in the Srf(CKO) mutant hearts. A requisite role for combinatorial cofactor interactions with SRF, as a major determinant for regulating the appearance of organized sarcomeres, was shown by viral rescue of SRF-null ES cells with SRF point mutants that block cofactor interactions. In the absence of SRF genes associated with biomineralization, GATA-6, bone morphogenetic protein 4 (BMP4), and periostin were strongly up-regulated, coinciding with the down regulation of many SRF dependent microRNA, including miR1, which exerted robust silencer activity over the induction of GATA-6 leading to the down regulation of BMP4 and periostin.
Niu et al. (2008) studied Cardiac development. Conditional serum response factor (SRF) knockout vs. Control was evaluated on Appearance of rhythmic beating myocytes and gene expression. Conditional knockout of serum response factor in the heart-forming region blocked the appearance of rhythmic beating myocytes and attenuated myofibril proteins while up-regulating biomineralization genes.