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

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

Speaker:  Dr Tiziana Bonaldi Department of Experimental Oncology, European Institute of Oncology, Milan

Host: Franca Fraternali

Abstract: Chromatin is a dynamic, well-organized and yet partially-defined protein-DNA-RNA structure that controls 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 and disease states. 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 a specific transcriptional state- or processes- on the underlying DNA.

However, the molecular details of its working mechanisms are only partially characterized and new approaches are needed to dissect the molecular code of epigenetic protein modifications in health and disease. Recent achievements made Mass Spectrometry (MS) and quantitative proteomics excellent tools to help understanding how histone and non-histonic PTMs mediate the structural-functional state of chromatin and modulate gene expression. 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.