The role of the H3K9 demethylase Jmjd1c in embryonic stem cell self-renewal and pluripotency

H3K9去甲基化酶Jmjd1c在胚胎干细胞自我更新和多能性中的作用

• 批准号: 195028861
• 负责人: Professor Dr. Mathias Treier
• 金额: --
• 依托单位: Max-Delbrück-Centrum für Molekulare Medizin (MDC) in der Helmholtz-Gemeinschaft
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/195028861?language=en
• 关键词: role; H3K9; demethylase; Jmjd1c; embryonic

In the first funding period of the SPP1356 we had proposed to study the role of Sall4 in maintaining embryonic stem cell pluripotency and self-renewal at the molecular and biochemical level. During the course of this study we have identified Rbpjk, the effector of the Notch pathway as a Sall4 interaction partner. Subsequent purification of the Rbpjk protein complex confirmed the Sall4/Rbpjk interaction. Furthermore ChIP-seq analysis for Sall4 and Rbpjk confirmed occupancy of common DNA loci throughout the genome. Furthermore, we could show that Sall4 directly regulates transcriptional activity of a Notch/Rbpkj response element providing a possible molecular explanation for the observed neural differentiation of ES cells upon Sall4 depletion (manuscript under review). Despite intensive work of many laboratories trying to identify Rbpjk interacting proteins, we have identified as novel interactor Jmjd1c, a putative histone H3K9 demethylase, that stoichiometrically associates with Rbpjk (see own research).The goal of this research proposal is to study the role of Jmjd1c in maintaining embryonic stem cell pluripotency and self-renewal at the molecular and biochemical level. This should enhance our understanding of epigenetic modifications underlying embryonic stem cell pluripotency and self-renewal in general and result into novel insights into the process of reprogramming of somatic genomes into a pluripotent or alternative cell fate.

在SPP 1356的第一个资助期内，我们建议在分子和生物化学水平上研究Sall 4在维持胚胎干细胞多能性和自我更新中的作用。在本研究的过程中，我们已经确定了Rbpjk，作为Sall 4相互作用伴侣的Notch途径的效应子。随后对Rbpjk蛋白复合物的纯化证实了Sall 4/Rbpjk相互作用。此外，对Sall 4和Rbpjk的ChIP-seq分析证实了整个基因组中常见DNA基因座的占用。此外，我们可以表明，Sall 4直接调节Notch/Rbpkj反应元件的转录活性，为在Sall 4耗尽后观察到的ES细胞的神经分化提供了可能的分子解释（正在审查的手稿）。尽管许多实验室的密集工作，试图确定Rbpjk相互作用的蛋白质，我们已经确定为新的相互作用Jmjd 1c，一个假定的组蛋白H3 K9去甲基化酶，与Rbpjk化学计量协会（见自己的研究）。这项研究计划的目标是研究Jmjd 1c在维持胚胎干细胞多能性和自我更新的分子和生化水平的作用。这将增强我们对胚胎干细胞多能性和自我更新的表观遗传修饰的理解，并导致对体细胞基因组重编程为多能性或替代细胞命运的过程的新见解。