Institut Jacques Monod Seminars – Till Bartke

Invited by the Duharcourt Lab, Till Bartke (Institute of Functional Epigenetics – Helmholtz Zentrum München) will present an Institut Jacques Monod Seminars on the theme:

Decoding chromatin states by proteomic profiling of modification-dependent nucleosome readers

Abstract:

DNA and histone modifications combine into characteristic patterns that demarcate functional regions of the genome. While many “readers” of individual modifications have been described, how composite modification signatures, histone variants, and inter-nucleosomal linkers are interpreted by the epigenetic machinery is still an open question. To obtain a comprehensive understanding of how chromatin readers decode complex chromatin states we have created a library of around 80 modified di-nucleosomes representing promoter, enhancer, and heterochromatin states using chemical biology approaches. We have used these di-nucleosomes in SILAC and label-free nucleosome affinity purifications to profile the interactions of ~2000 nuclear proteins with the different modification states by quantitative proteomics. Systematic quantification of their binding to the differently modified di-nucleosomes using tailored computational analysis methods has enabled us to predict modification features recognised by several hundred chromatin readers and to identify networks of co-regulated proteins, thereby allowing us to describe complex chromatin modification read-outs at a large scale. Apart from highly distinctive binding responses to different modification features, we find that many factors recognise multiple features and that nucleosomal modifications and linker DNA operate largely independently in recruiting proteins to chromatin. To make the data easily accessible, we have developed the interactive online resource MARCS (the ‘Modification Atlas of Regulation by Chromatin States’) which provides computational tools to analyse and visualise the data. Our results bridge the gap between chromatin states and chromatin readers, and through MARCS we provide a valuable information source to the community to further advance the discovery of fundamental principles of genome regulation.

Biosketch – Till Bartke

Till Bartke is the Deputy Director of the Institute of Functional Epigenetics (IFE) at Helmholtz Munich (Germany). He has a long-standing interest in the epigenetic regulation of chromatin by chemical modifications of histone proteins and the DNA. After completing his PhD at the Max Planck Institute of Biochemistry in Martinsried (Germany) under the supervision of Stefan Jentsch and postdoctoral research with Tony Kouzarides at the Gurdon Institute at the University of Cambridge (UK), Till established his own group at the MRC Laboratory of Medical Sciences, Imperial College London (UK). He joined the IFE as Deputy Director in April 2017. Till’s research combines chemical biology, quantitative proteomics, genomics, and computational approaches to investigate the cellular functions of readers of complex epigenetic modification signatures at molecular and systems-wide scales.