Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada.
Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada
Development. 2019 Apr 1;146(7):dev170498. doi: 10.1242/dev.170498.
Murine cardiac and hematopoietic progenitors are derived from mesoderm. Cdx function impacts both yolk sac hematopoiesis and cardiogenesis in zebrafish, suggesting that Cdx family members regulate early mesoderm cell fate decisions. We found that Cdx2 occupies a number of transcription factor loci during embryogenesis, including key regulators of both cardiac and blood development, and that Cdx function is required for normal expression of the cardiogenic transcription factors and Furthermore, Cdx and Brg1, an ATPase subunit of the SWI/SNF chromatin remodeling complex, co-occupy a number of loci, suggesting that Cdx family members regulate target gene expression through alterations in chromatin architecture. Consistent with this, we demonstrate loss of Brg1 occupancy and altered chromatin structure at several cardiogenic genes in Cdx-null mutants. Finally, we provide evidence for an onset of Cdx2 expression at E6.5 coinciding with egression of cardiac progenitors from the primitive streak. Together, these findings suggest that Cdx functions in multi-potential mesoderm to direct early cell fate decisions through transcriptional regulation of several novel target genes, and provide further insight into a potential epigenetic mechanism by which Cdx influences target gene expression.
鼠类心脏和造血祖细胞来源于中胚层。Cdx 功能影响斑马鱼的卵黄囊造血和心脏发生，表明 Cdx 家族成员调节早期中胚层细胞命运决定。我们发现 Cdx2 在胚胎发生过程中占据许多转录因子基因座，包括心脏和血液发育的关键调节因子，并且 Cdx 功能对于心脏发生转录因子 和 的正常表达是必需的。此外，Cdx 和 Brg1，SWI/SNF 染色质重塑复合物的 ATP 酶亚基，共同占据许多基因座，表明 Cdx 家族成员通过改变染色质结构来调节靶基因表达。与此一致，我们证明在 Cdx 缺失突变体中，几个心脏发生基因的 Brg1 占据和染色质结构发生改变。最后，我们提供了 E6.5 时 Cdx2 表达开始的证据，这与心脏祖细胞从原始条纹中迁出相吻合。总之，这些发现表明 Cdx 在多潜能中胚层中发挥作用，通过几个新靶基因的转录调控来指导早期细胞命运决定，并进一步深入了解 Cdx 影响靶基因表达的潜在表观遗传机制。
