Objetivo
Proper and controlled expression of genes is essential for normal cell growth. Chromatin modifying enzymes play a
fundamental role in the control of gene expression and their deregulation is often linked to cancer. In recent years chromatin
modifiers have been considered key targets for cancer therapy and this demands a full understanding of their biological
functions. Previous biochemical and structural studies have focused on the identification of chromatin modifying enzymes
and characterization of their substrate specificities and catalytic mechanisms. However, a comprehensive view of the
biological processes, signaling pathways and regulatory circuits in which these enzymes participate is missing. Protein
arginine methyltransferases (PRMTs), which methylate histones and are evolutionarily conserved from yeast to human,
constitute an example of chromatin modifying enzymes whose functional and regulatory networks remain unexplored. I
propose to use complementary state-of-the-art genomic and proteomic approaches in order to identify the protein networks
and cellular pathways that are linked to PRMTs. In parallel, I will identify novel regulatory circuits and define the molecular
mechanisms that control methylation of specific histone arginine residues. I will utilize the yeast S. cerevisiae as a model
organism because it allows genetic, biochemical and genomic approaches to be combined. Most importantly, many of the
pathways and mechanisms in yeast are highly conserved and therefore, the findings from this study will be pertinent to
human and other eukaryotic organisms. Establishing a global cellular wiring diagram of PRMTs will serve as a paradigm for
other chromatin modifiers and is imperative for assessing the efficacy of these enzymes as therapeutic targets.
Ámbito científico
Convocatoria de propuestas
ERC-2010-StG_20091118
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Régimen de financiación
ERC-SG - ERC Starting GrantInstitución de acogida
1678 Nicosia
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