Research on Gene Expression Network via histone acetylation

组蛋白乙酰化基因表达网络研究

基本信息

批准号：
12557018
负责人：
ISHII Shunsuke
金额：
$ 8.32万
依托单位：
THE INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

We have generated and analysed the mutant mice lacking transcription factor Shn-2. Shn-2 was originally identified by our group as a factor that binds to the NF-KB site, and a large protein of 270 kD with two metal-finger structures. Since Drosophila homologue of Shn acts in the dpp signaling pathway, vertebrate Shn is thought to act in the BMP/TGFβ/activin signaling pathway. Shn-2-deficient mice seems to be healthy, but have a defects of T-cell development. In the thimi of Shn-2 mutant mice, almost no single-positive T cells were observed. A series of analyses indicated that Shn-2 is essential for the positive selection of T ceils. These results suggest that the BMP/TGFβ/activin signaling pathway plays some role in the T cell development.We have also analysed the physiological role of Ski by using the Ski-deficient mice. We treated the Ski heterozygous mutant mice with chemical carcinogen DMBA. No tumors were generated in wild-type mice, whereas significant numbers of Ski heterozygotes developed the tumors such as T- and B-cell lymphomas. Further, the mouse fibroblasts prepared from the Ski-deficient embryos had increased proliferative capacity compared to wild-type cells. In addition, the introduction of activated Ki-ras into Ski-deficient mouse embryonic fibroblasts resulted in neoplastic transformation. These finding demonsrrate that Ski acts as a tumor suppressor in some types of cells.

我们已经生成并分析了缺乏转录因子SHN-2的突变小鼠。 SHN-2最初被我们的组识别为与NF-KB位点结合的因素，并且具有两个金属手指结构的270 kD的大蛋白质。由于SHN的果蝇同源物在DPP信号通路中起作用，因此脊椎动物SHN被认为在BMP/TGFβ/激活素信号通路中起作用。 SHN-2缺陷小鼠似乎很健康，但具有T细胞发育的缺陷。在SHN-2突变小鼠的THIMI中，几乎没有观察到单阳性T细胞。一系列分析表明，SHN-2对于t层的阳性选择至关重要。这些结果表明，BMP/TGFβ/激活素信号通路在T细胞发育中起着一定作用。我们还通过使用SKI-DIFIC小鼠分析了SKI的物理作用。我们用化学致癌DMBA治疗了滑雪杂合突变小鼠。在野生型小鼠中没有产生肿瘤，而大量的滑雪杂合子则会产生肿瘤，例如T-和B细胞淋巴瘤。此外，与野生型细胞相比，从滑雪型胚胎制备的小鼠成纤维细胞具有增加的增殖能力。另外，将活化的Ki-Ras引入缺乏滑雪的小鼠胚胎成纤维细胞导致肿瘤转化。这些发现，在某些类型的细胞中，滑雪术充当肿瘤抑制因子。