Record #243385 - GSI Repository

EPIDNA

Structural investigation of interplay between epigenetics, transcriptional regulation and DNA damage

Grant period	2020-04-01 - 2022-03-31
Funding body	European Union
Call number	H2020-MSCA-IF-2019
Grant number	894489
Identifier	G:(EU-Grant)894489

Note: In eukaryotic cells, gene expression is regulated by a complex interplay between a number of factors, from large-scale chromatin accessibility to inducible enhancers or repressors to local DNA modifications, changes in nucleosome architecture and specific histone markers. These finely tuned factors coordinate embrional development, response to stimuli and changes in cell fate. At the same time, this regulatory network has to robustly accommodate random events, most notably the presence of DNA damage and the action of DNA repair factors. While recent reports suggest this interplay is not always smooth, our mechanistic understanding of the underlying processes is severely limited, highlighting the need for quantitative approaches that will yield predictive models. In this proposal, I plan to investigate three aspects of this interplay that recently came into the spotlight. Firstly, an integrative computational and experimental approach will be used to quantify the positioning effect resulting from a range of common DNA modifications: regulatory base variants that can be used to enforce specific nucleosome patterns, and damage byproducts that would thereby interfere with DNA repair through altered exposure to the environment. Secondly, a number of transcription factors will be systematically assessed to detect ones sensitive to the presence of the most common oxidative lesion, 8-oxoguanine, to identify possible direct cross-talk between oxidative stress and transcriptional regulation at oxidative hot spots. Finally, a multiscale quantum/classical study will explore the thermodynamics, mechanism of formation and possible nucleosomal locations of covalent histone-DNA cross-links that were recently postulated to both mediate the regulatory role of 5-formylcytosine and accelerate strand scission at abasic sites.

Recent Publications

There are no publications

Record created 2021-10-10, last modified 2023-02-12

Similar records

Add to personal basket
Export as Author List with IDs BibTeX (UTF-8), EndNote XML, EndNote Text, RIS, MARC, Print MARC, MARCXML, DC,
Request correction
Submit fulltext

GSI Homepage \| GSI Library \| English Deutsch \| guest :: login GSI Repository
Search	Submit	Personalize Your alerts Your baskets Your searches	Help