Methylation on and beyond histones, in health and disease mechanisms: a proteomic view

Venue: Povo 2 - room B101
Time: 2.30 pm

Speaker:

• Tiziana Bonaldi - Department of Experimental Oncology, European Institute of Oncology, Milan

Abstract:

Chromatin is a dynamic nucleoprotein complex controlling various DNA-dependent processes. A large number of site-specific post-translational modifications of histones (hPTMs) contribute to the maintenance and modulation of chromatin plasticity, gene activation, DNA replication and repair, and a variety of other biological processes. The observation of the diversity, frequency and co-occurrence of hPTMs at distinct genomic loci led to the notion that these marks create a molecular barcode, read by effector proteins that translate it into specific functional outcomes. This language is often altered in disease, especially cancer.

The molecular details of this epigenetic code are only partially characterized and new approaches are needed to dissect them in physiological conditions and to understand how they are distorted during tumorigenesis. Recent achievements have made Mass Spectrometry (MS) and quantitative proteomics excellent tools to help understanding how histone PTMs mediate the structural-functional state of chromatin and modulate gene expression, both in health and disease. My team contributed to the field by setting-up distinct MS-proteomics strategies to investigate chromatin plasticity and nuclear dynamics governed by post-translational modifications, on and beyond histones.

In this talk, I will walk through to these strategies, with a special emphasis on: the MS-based epigenome mapping of cancer patient samples to identify PTMs signature with potential as biomarker; the proteomic dissection of cis-regulatory chromatin regions during inflammation; the exploration of the methyl-proteome beyond chromatin and of its functional implication in nuclear dynamics.