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ChemEpigen SIGNED

The chemical understanding of biomolecular recognition in epigenetics

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Project "ChemEpigen" data sheet

The following table provides information about the project.

Coordinator
SYDDANSK UNIVERSITET 

Organization address
address: CAMPUSVEJ 55
city: ODENSE M
postcode: 5230
website: www.sdu.dk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Denmark [DK]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-STG
 Funding Scheme ERC-STG
 Starting year 2017
 Duration (year-month-day) from 2017-04-01   to  2022-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    SYDDANSK UNIVERSITET DK (ODENSE M) coordinator 1˙266˙890.00
2    STICHTING KATHOLIEKE UNIVERSITEIT NL (NIJMEGEN) participant 233˙110.00

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 Project objective

The ultimate aim of this ERC project is to provide a comprehensive and complete understanding, at the atomic-level of sophistication, of genuinely important biomolecular recognition processes in epigenetics that play key roles in human health and disease. At the biochemical level, epigenetics refers to mechanisms, such as enzymatic modifications of DNA and posttranslational modifications of the associated histone proteins, that regulate the activity of human genes. The proposed work aims to address epigenetics using the physical-organic chemistry approach that enables the elucidation of the elemental processes with unprecedented molecular/atomic detail. The project will experimentally and computationally examine non-covalent interactions between three essential constituents of the epigenetic biomolecular system, namely epigenetic proteins, histones and water, at the level of short histone peptides, intact histone proteins, the nucleosome assembly and nucleosome arrays. Our programme, built on synergistic thermodynamic, structural and computational studies, aims to unravel i) the underlying chemical origin of methyllysine-containing histones in epigenetics, ii) the chemical basis for the recognition of methylarginine-containing histones in epigenetic processes, and iii) the role of unstructured histone tails in biomolecular recognition, which together form the three main structural elements found in the epigenetic framework. Results from this work will be important from both a fundamental molecular perspective as well as from the biomedical perspective, because proteins involved in epigenetic regulation processes are currently regarded as important targets for numerous therapeutic interventions, most notably for cancer treatment.

 Publications

year authors and title journal last update
List of publications.
2020 Abbas H. K. Al Temimi, Paul B. White, Marcus J. M. Mulders, Nicole G. A. van der Linden, Richard H. Blaauw, Anita Wegert, Floris P. J. T. Rutjes, Jasmin Mecinović
Methylation of geometrically constrained lysine analogues by histone lysine methyltransferases
published pages: 3039-3042, ISSN: 1359-7345, DOI: 10.1039/c9cc09098c
Chemical Communications 56/20 2020-03-24
2020 Abbas H. K. Al Temimi, Vu Tran, Ruben S. Teeuwen, Arthur J. Altunc, Helene I. V. Amatdjais-Groenen, Paul B. White, Danny C. Lenstra, Giordano Proietti, Yali Wang, Anita Wegert, Richard H. Blaauw, Ping Qian, Wansheng Ren, Hong Guo, Jasmin Mecinović
Examining sterically demanding lysine analogs for histone lysine methyltransferase catalysis
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-020-60337-3
Scientific Reports 10/1 2020-03-24
2019 Abbas H. K. Al Temimi, Renate van der Wekken-de Bruijne, Giordano Proietti, Hong Guo, Ping Qian, Jasmin Mecinović
γ-Thialysine versus Lysine: An Insight into the Epigenetic Methylation of Histones
published pages: 1798-1804, ISSN: 1043-1802, DOI: 10.1021/acs.bioconjchem.9b00313
Bioconjugate Chemistry 30/6 2020-02-19
2019 Bas J. G. E. Pieters, Jordi C. J. Hintzen, Yvonne Grobben, Abbas H. K. Al Temimi, Jos J. A. G. Kamps, Jasmin Mecinović
Installation of Trimethyllysine Analogs on Intact Histones via Cysteine Alkylation
published pages: 952-958, ISSN: 1043-1802, DOI: 10.1021/acs.bioconjchem.9b00065
Bioconjugate Chemistry 30/3 2020-02-19
2019 Abbas H. K. Al Temimi, Helene I. V. Amatdjais-Groenen, Y. Vijayendar Reddy, Richard H. Blaauw, Hong Guo, Ping Qian, Jasmin Mecinović
The nucleophilic amino group of lysine is central for histone lysine methyltransferase catalysis
published pages: 112, ISSN: 2399-3669, DOI: 10.1038/s42004-019-0210-8
Communications Chemistry 2/1 2020-02-19
2017 Roman Belle, Abbas H. K. Al Temimi, Kiran Kumar, Bas J. G. E. Pieters, Anthony Tumber, James E. Dunford, Catrine Johansson, Udo Oppermann, Tom Brown, Christopher J. Schofield, Richard J. Hopkinson, Robert S. Paton, Akane Kawamura, Jasmin Mecinović
Investigating d -lysine stereochemistry for epigenetic methylation, demethylation and recognition
published pages: 13264-13267, ISSN: 1359-7345, DOI: 10.1039/c7cc08028j
Chemical Communications 53/99 2020-02-19
2018 Abbas H. K. Al Temimi, Roman Belle, Kiran Kumar, Jordi Poater, Peter Betlem, Bas J. G. E. Pieters, Robert S. Paton, F. Matthias Bickelhaupt, Jasmin Mecinović
Recognition of shorter and longer trimethyllysine analogues by epigenetic reader proteins
published pages: 2409-2412, ISSN: 1359-7345, DOI: 10.1039/c8cc01009a
Chemical Communications 54/19 2020-02-19

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