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

• Applicant: Professor Dr. Mathias Treier
• Subject Area: Cell Biology ; Developmental Biology
• Term: from 2011 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 195028861

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.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1356: Pluripotency and Cellular Reprogramming