Characterisation of novel nuclear substrates of protein arginine methyltransferases and the mechanisms of chromatin regulation by arginine methylation

• Applicant: Professorin Dr. Uta-Maria Bauer
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2004 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5470729

Posttranslational modifications of histones and other chromatin proteins, like acetylation, phosphorylation and methylation, play a fundamental role in the regulation of chromatin structure and gene expression. According to their importance in proliferation, differentiation and apoptosis, mutation of chromatin modifying enzymes is involved in the generation of cancer and other diseases. Whereas the transcriptional function of lysine acetylation and lysine methylation of chromatin proteins has been well documented, the consequences and precise molecular mechanisms of arginine methylation are still obscure. Among the seven protein arginine methyltransferases (PRMTs) in mammals, three family members, PRMT1, PRMT4 and PRMT5, have been shown to methylate and to regulate proteins involved in the establishment of chromatin structure and regulation of transcription respectively. Histones H3 and H4, the transcription factor STAT1, the transcription elongation factor Spt5 and the histone acetyltransferase CBP/p300 are known substrates of these PRMTs. This project aims (i) to identify novel nuclear substrates of PRMTs from mammalian cell lines, which are involved in the regulation of gene expression, and (ii) to analyse how these modifications are recognised and translated into downstream signalling events, which cause functional changes of the modified targets and alteration of chromatin structure and chromatin dependent processes.

• DFG Programme: Research Units
• Subproject of: FOR 531: Chromatin Mediated Biological Decisions