| First Author | Gregoire S | Year | 2013 |
| Journal | Circ Res | Volume | 112 |
| Issue | 6 | Pages | 900-10 |
| PubMed ID | 23307821 | Mgi Jnum | J:212854 |
| Mgi Id | MGI:5582355 | Doi | 10.1161/CIRCRESAHA.113.259259 |
| Citation | Gregoire S, et al. (2013) Essential and unexpected role of Yin Yang 1 to promote mesodermal cardiac differentiation. Circ Res 112(6):900-10 |
| abstractText | RATIONALE: Cardiogenesis is regulated by a complex interplay between transcription factors. However, little is known about how these interactions regulate the transition from mesodermal precursors to cardiac progenitor cells (CPCs). OBJECTIVE: To identify novel regulators of mesodermal cardiac lineage commitment. METHODS AND RESULTS: We performed a bioinformatic-based transcription factor binding site analysis on upstream promoter regions of genes that are enriched in embryonic stem cell-derived CPCs. From 32 candidate transcription factors screened, we found that Yin Yang 1 (YY1), a repressor of sarcomeric gene expression, is present in CPCs in vivo. Interestingly, we uncovered the ability of YY1 to transcriptionally activate Nkx2.5, a key marker of early cardiogenic commitment. YY1 regulates Nkx2.5 expression via a 2.1-kb cardiac-specific enhancer as demonstrated by in vitro luciferase-based assays, in vivo chromatin immunoprecipitation, and genome-wide sequencing analysis. Furthermore, the ability of YY1 to activate Nkx2.5 expression depends on its cooperative interaction with Gata4 at a nearby chromatin. Cardiac mesoderm-specific loss-of-function of YY1 resulted in early embryonic lethality. This was corroborated in vitro by embryonic stem cell-based assays in which we showed that the overexpression of YY1 enhanced the cardiogenic differentiation of embryonic stem cells into CPCs. CONCLUSIONS: These results demonstrate an essential and unexpected role for YY1 to promote cardiogenesis as a transcriptional activator of Nkx2.5 and other CPC-enriched genes. |
