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Functional dissection of epigenetic modifications of histones during development of the central nervous system

Precursor cells residing in ventricular and subventricular zones give rise to the adult cerebral cortex that consists of six layers formed in an “inside-out manner” during development. Functionally specialized areas of the neocortex are formed through a gradient of gene expression in the neuroepithelium. This relies on a time-dependent cell fate decision of precursor cells. We have highlighted the contribution of histone methylation in the neuronal specification of upper layer neurons in an Af9-mutant mouse. Af9-interaction partner Dot1l regulates the expression of the transcription factor Tbr1 through methylation of Histone H3 at position K79. Our interests are to further elucidate the transcriptional network of Af9 and Dot1l and their implication in CNS development. Thereby, we are analysing different neuroanatomical structures such as the cerebral cortex, hippocampus, cerebellum and spinal cord, all of which are affected after loss of either Af9 or Dot1l. Our attempts include the analyses of the epigenomes, cistromes, transcriptomes, proteomes and interactomes of Af9 and Dot1l in embryonic stem cells and committed neural progenitor cells. Our aim is to elucidate • how epigenetic modifications are involved in neural stem cell fate decision • how epigenetic modifications control the cell cycle of neural stem cells • how epigenetic modifications are changing during neuronal differentiation

Ansprechpartner: Prof. Dr. Tanja Vogel
Tel: 0761/203-5087
Email: tanja.vogel@anat.uni-freiburg.de
Projektbeginn: 2011
Projektende: (unbegrenzt)
Vogel T

Albert-Ludwigs-Universität Freiburg

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