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Involvement of MCAF1-MBD1 complex in hererochromatin formation and nuclear atypia. (2006)

MCAF1-MBD1 复合物参与异染色质形成和核异型性。

基本信息

批准号：
18591839
负责人：
ICHIMURA Takaya
金额：
$ 2.57万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591839/
关键词：
heterochromatin DNA methylation cervical cancer 核異型

项目摘要

1. We demonstrate that modification of MBD1 with either SUMO-2/3 or SUMO-1 facilitated the interaction between MBD1 and MCAF1. SUMOs directory interact with human MCAF1-SETDB1 complex. Specific knockdown of either SUMO-2/3 or SUMO-1 induced dissociation of MCAF1, trymethyl-H3-K9, and the HP1 proteins from the MBD1-containing heterofhromatin foci. These findings provide insights into the roles of SUMOylation in the regulation of the MBD1-MCAF1 mediated heterochromatin formation and gene silencing. (J. Biol. Chem. 281:23180-23190)2. We demonstrate that MCAF1 is found to be frequently overexpressed in naturally occurring cancers that orignnate in different tissues. We report that MCAF1 is involved in Sp1-dependent maintenance of telomerase activity in cancer cells. (J.Biol.Chem.284 : 5165-5174)3. We report that the DNA methylation-mediated repressor MBD1 interacts with Ring1b and hPc2, the major components of Polycomb repressive complex. MBD1 and hPC2 cooperate for transcriptional repression of HOXAgene. We also suggest that MBD1 and Polycomb group protains have overlapping roles in epigenetic gene silencing and heterochromatin foci formation through their interaction. (J.Biol.Chem.282 : 16391-400)4. We analyzed the expression level of MCAF1 in cervical cancer tissues. MCAF1 is found to be overexpressed in most of cervical cancer tissues and not to be found in normal cervical tissues. We are now investigating about the possibility of MCAF1 as a maker of cervical cancers.

1. 我们证明用SUMO-2/3或SUMO-1修饰MBD1可以促进MBD1和MCAF1之间的相互作用。sumo目录与人类MCAF1-SETDB1复合体相互作用。特异性敲低SUMO-2/3或SUMO-1诱导MCAF1、trymethyl-H3-K9和HP1蛋白从含有mbd1的异染色质灶中分离。这些发现为SUMOylation在调节MBD1-MCAF1介导的异染色质形成和基因沉默中的作用提供了见解。(生物。化学281:23180 - 23190)2。我们发现MCAF1在自然发生的不同组织的癌症中经常过表达。我们报道MCAF1参与癌细胞中端粒酶活性的sp1依赖性维持。(J.Biol.Chem。[au:] 2。我们报道DNA甲基化介导的抑制因子MBD1与Polycomb抑制复合物的主要成分Ring1b和hPc2相互作用。MBD1和hPC2协同抑制HOXAgene的转录。我们还认为MBD1和Polycomb蛋白通过相互作用在表观遗传基因沉默和异染色质病灶形成中具有重叠作用。(J.Biol.Chem。3 .中文翻译：我们分析了MCAF1在宫颈癌组织中的表达水平。MCAF1在大多数宫颈癌组织中被发现过表达，而在正常宫颈组织中未被发现。我们现在正在调查MCAF1作为宫颈癌致病因子的可能性。