First Author | Beketaev I | Year | 2016 |
Journal | Dev Dyn | Volume | 245 |
Issue | 3 | Pages | 379-87 |
PubMed ID | 26384464 | Mgi Jnum | J:229171 |
Mgi Id | MGI:5751005 | Doi | 10.1002/dvdy.24349 |
Citation | Beketaev I, et al. (2016) cis-regulatory control of Mesp1 expression by YY1 and SP1 during mouse embryogenesis. Dev Dyn 245(3):379-87 |
abstractText | BACKGROUND: Mesp1 is critical for early cardiomyocyte differentiation and heart development. We previously observed down-regulation of Mesp1 expression in YY1-ablated mouse embryonic hearts. However, how Mesp1 expression is mediated by YY1 is not well understood. RESULTS: We excised YY1 in the murine embryos using Sox2-cre and found that Mesp1 was down-regulated in the embryonic day (E) 7.5 mutant embryos. Also, YY1 activated the 6 kb Mesp1 regulatory element fused to a luciferase reporter. We identified two putative YY1 binding sites in the proximal promoter region of Mesp1 gene, and found that mutation of these sites significantly reduced YY1-induced activation of the Mesp1 promoter. We also uncovered one cognitive site for SP1, one of the earliest binding partners of YY1 identified. Mutation of this SP1 site repressed SP1-induced activation of the Mesp1 promoter. Moreover, YY1 and SP1 synergistically activated the Mesp1 promoter. Consistently, while Lacz expression driven by the wild-type 6 kb regulatory element of Mesp1 gene was robust in E7.5 mouse embryos, the mutation of these binding sites in the context of this 6 kb sequence substantially reduced the LacZ expression during embryogenesis. CONCLUSIONS: YY1 and SP1 independently and cooperatively govern the Mesp1 expression during embryogenesis. Developmental Dynamics 245:379-387, 2016. (c) 2015 Wiley Periodicals, Inc. |