Replication and translation of epigenetic information

表观遗传信息的复制和翻译

• 批准号: 5407439
• 负责人: Professorin Dr. Maria Cristina Cardoso
• 金额: --
• 依托单位: Arbeitsgruppe Cell Biology and Epigenetics
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2003
• 资助国家: 德国
• 起止时间: 2002-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5407439?language=en
• 关键词: Replication; translation; epigenetic; information

Methyl-cytosine binding proteins (MeCPs) play a central role in the mediation of epigenetic effects. They bind to methylated sites in the DNA, recruit histone deacetylases (HDACs9 which may then cause chromatin condensation and transcriptional silencing. We have previously studied the dynamics of DNA replication in living mammalian cells using fluorescence labeling and bleaching techniques. We want to extend this work now to the re-establishment of chromatin structures (duplication of epigenetic information) on the newly synthesized DNA strand and investigate the turn-over and interaction of MeCPs in the postreplicative reassembly of chromatin. These studies should elucidate whether MeCPs bind stably to chromatin or whether they are in constant flux, which would facilitate the dynamic modulation of chromatin states. We have recently observed that the expression level of a member of this family, MeCP2, has a profound effect on the spatial organization of the genome in living cells. We will investigate which functional domains of MeCP2 are involved in this large scale reorganization and whether other family members show similar effects. We will later investigate whether this chromatin reorganisation does also effect gene expression. These studies should help to elucidate how MeCPs mediate and regulate epigenetic effects.

甲基胞嘧啶结合蛋白（MeCPs）在介导表观遗传效应中起着重要作用。它们与DNA中的甲基化位点结合，募集组蛋白脱乙酰酶（HDACs）9，然后可能导致染色质浓缩和转录沉默。我们以前研究了动态的DNA复制在活的哺乳动物细胞中使用荧光标记和漂白技术。我们现在希望将这项工作扩展到在新合成的DNA链上重建染色质结构（表观遗传信息的复制），并研究MeCP在染色质复制后重组中的翻转和相互作用。这些研究应该阐明MeCP是否稳定地结合到染色质上，或者它们是否处于恒定的通量中，这将有助于染色质状态的动态调节。我们最近观察到，该家族成员MeCP2的表达水平对活细胞中基因组的空间组织具有深远的影响。我们将研究MeCP2的哪些功能域参与了这种大规模重组，以及其他家族成员是否表现出类似的作用。我们稍后将研究这种染色质重组是否也影响基因表达。这些研究将有助于阐明MeCPs如何介导和调节表观遗传效应。