| First Author | Niu Z | Year | 2008 |
| Journal | Proc Natl Acad Sci U S A | Volume | 105 |
| Issue | 46 | Pages | 17824-9 |
| PubMed ID | 19004760 | Mgi Jnum | J:321574 |
| Mgi Id | MGI:6887594 | Doi | 10.1073/pnas.0805491105 |
| Citation | Niu Z, et al. (2008) Serum response factor orchestrates nascent sarcomerogenesis and silences the biomineralization gene program in the heart. Proc Natl Acad Sci U S A 105(46):17824-9 |
| abstractText | 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. |
