首页 | 本学科首页   官方微博 | 高级检索  
   检索      


The Cohesin loading factor NIPBL recruits histone deacetylases to mediate local chromatin modifications
Authors:Jahnke Philipp  Xu Weizhen  Wülling Manuela  Albrecht Melanie  Gabriel Heinz  Gillessen-Kaesbach Gabriele  Kaiser Frank J
Institution:Philipp Jahnke, Weizhen Xu, Manuela Wülling, Melanie Albrecht, Heinz Gabriel, Gabriele Gillessen-Kaesbach, and Frank J. Kaiser
Abstract:Cornelia de Lange Syndrome (CdLS) is a rare congenital malformation disorder. About half of the patients with CdLS carry mutations in the NIPBL gene encoding the NIPBL protein, a subunit of the Cohesin loading complex. Recent studies show association of Cohesin with chromatin-remodeling complexes, either by establishing cohesion or by recruiting Cohesin to specific chromosome locations. In yeast two-hybrid assays, we identified an interaction of NIPBL with the histone deacetylases -1 and -3. These interactions were confirmed in mammalian cells by coimmunoprecipitation and a critical region for interaction was defined to a stretch of 163 amino acids of a highly conserved region of NIPBL, which is mutated in patients with CdLS. Utilizing reporter gene assays, we could show that NIPBL fused to the GAL4-DNA-binding domain (GAL4-DBD) represses promoter activity via the recruitment of histone deacetylases. Interestingly, this effect is dramatically reduced by both NIPBL missense mutations identified in CdLS and by chemical inhibition of the histone deacetylases. Our data are the first to indicate a molecular and functional connection of NIPBL with chromatin-remodeling processes via the direct interaction with histone deacetylases.
Keywords:
本文献已被 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号