Piceatannol attenuates cardiac hypertrophy in an animal model through regulation of the expression and binding of the transcription factor GATA binding factor 6

Piceatannol is found in grapes, passion fruit, and Japanese knotweed. Piceatannol pretreatment suppresses cardiac hypertrophy induced by isoproterenol as assessed by heart weight/body weight ratio, cross-sectional area, and expression of hypertrophic markers. The anti-hypertrophic effect of piceatannol in rat neonatal cardiomyocytes is the same as that in vivo. Piceatannol inhibits lentiviral-GATA6-induced cardiomyocyte hypertrophy. Furthermore, piceatannol reduces the interaction between GATA4 and GATA6 as well as the DNA-binding activity of endogenous GATA6 in the ANP promoter. Our results suggest that piceatannol may be a novel therapeutic agent for the prevention of cardiac hypertrophy.Structured summary of protein interactionsGATA6 physically interacts with GATA4 by anti V5 tag coimmunoprecipitation (View interaction)     

The expression of CKLFSF2B is regulated by GATA1 and CREB in the Leydig cells,which modulates testicular steroidogenesis

CKLFSF is a protein family that serves as a functional bridge between chemokines and members of the transmembrane 4 superfamily (TM4SF). In the course of evolution, CKLFSF2 has evolved as two isoforms, namely CKLFSF2A and CKLFSF2B, in mice. CKLFSF2A, also known as CMTM2A and ARR19, is expressed in the testis and is important for testicular steroidogenesis. CKLFSF2B is also known to be highly expressed in the testis. In the prepubertal stage, CKLFSF2B is expressed only in Leydig cells, but it is highly expressed in haploid germ cells and Leydig cells in adult testis. CKLFSF2B is naturally processed inside the cell at its C-terminus to yield smaller proteins compared to its theoretical size of ≈25?kDa. The Cklfsf2b gene is regulated by GATA-1 and CREB protein, binding to their respective binding elements present in the 2-kb upstream promoter sequence. In addition, the overexpression of CKLFSF2B inhibited the activity of the Nur77 promoter, which consequently represses the promoter activity of Nur77-target steroidogenic genes such as P450c17, 3β-HSD, and StAR in MA-10 Leydig cells. Adenovirus-mediated overexpression of CKLFSF2B in primary Leydig cells isolated from adult mice shows a repression of steroidogenic gene expression and consequently testosterone production. Moreover, intratesticular injection of CKLFSF2B-expressing adenovirus in adult mice clearly had a repressive effect compared to the control injected with only GFP-expressing adenovirus. Altogether, these findings suggest that CKLFSF2B might be involved in the development and function of Leydig cells and regulate testicular testosterone production by fine-tuning the expression of steroidogenic genes.     

位点控制区(LCR)调控基因表达的研究进展

最早在人类β珠蛋白基因座中发现的位点控制区(locus control regions,LCR)对于珠蛋白基因在红细胞分化和发育过程中的特异性表达起着重要作用。LCR位于珠蛋白基因上游6～25 kb,由至少7个DNaseⅠ超敏感位点所组成,具有很强的增强子活性,可以激活和促进珠蛋白基因的转录。LCR增强子活性具有组织特异性,并与拷贝数成正比。此外,LCR还参与基因在细胞核内的定位、组蛋白修饰、染色质开放、边界结构域形成,以及DNA复制起始等精细调控过程。有多个模型阐述LCR远程调控基因表达的分子机制,被普遍接受的是成环模型(looping model)。在生长激素(GH)、T_H2细胞因子、MHCⅡ等基因区域也发现有类似珠蛋白的LCR结构,都在深入研究之中。