A crucial role of a high mobility group protein HMGA2 in cardiogenesis
The high mobility group (HMG) of nuclear proteins regulates expression of many genes through architectural remodelling of the chromatin structure, and formation of multiprotein complexes on promoter/enhancer regions. This leads to the active transcription of their target genes. Here we show that HMGA2, a member of the HMGA sub-family of HMG proteins, has a critical function in cardiogenesis. Overexpression of HMGA2 enhanced, whereas siRNA-mediated knockdown of HMGA2 blocked, cardiomyocyte differentiation of the embryonal carcinoma cell line P19CL6. Moreover, overexpression of a dominant-negative HMGA2 or morpholino-mediated knockdown of HMGA2 expression blocked normal heart formation in Xenopus laevis embryos, suggesting that HMGA2 has an important role in cardiogenesis both in vitro and in vivo. Mechanistically, HMGA2 associated with Smad1/4 and showed synergistic trans-activation of the gene for a cardiac transcription factor Nkx2.5; a conserved HMGA2 binding site was required for the promoter activity of Nkx2.5 gene, both in P19CL6 cells and in transgenic Xenopus embryos. Thus, HMGA2 is a positive regulator of Nkx2.5 gene expression and is essential for normal cardiac development.
The historic takeover of Fannie Mae and Freddie Mac, which could come as soon as this weekend, moved to the forefront of the presidential campaign Saturday.
In the arena that night, the whole last minute was drowned out by cheers — and then when the soaring music swelled, the confetti rained down as the harbinger of balloons and the hopeful first family took the stage, forget about it — it was a perfect end to a convention that last Monday, no one even knew if it would happen. But it did, and I'm so glad to have been there.
