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MaintainMeth SIGNED

Quantitative analysis of DNA methylation maintenance within chromatin

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EC-Contrib. €

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Project "MaintainMeth" data sheet

The following table provides information about the project.

Coordinator
JOHN INNES CENTRE 

Organization address
address: NORWICH RESEARCH PARK COLNEY
city: NORWICH
postcode: NR4 7UH
website: www.jic.bbsrc.ac.uk

contact info
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surname: n.a.
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 Coordinator Country United Kingdom [UK]
 Total cost 2˙749˙962 €
 EC max contribution 2˙749˙962 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 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    JOHN INNES CENTRE UK (NORWICH) coordinator 2˙749˙962.00

Map

 Project objective

Cytosine methylation is a chemical modification that is precisely copied when DNA is replicated. Because methylation can regulate gene expression, accurate reproduction of DNA methylation patterns is essential for plant and animal development and for human health. The enzymes that maintain DNA methylation have to work within chromatin, and particularly to contend with nucleosomes – tight complexes of DNA and histone proteins. How methylation of nucleosomal DNA is maintained remains unknown, and even the simple matter of whether nucleosomes hinder or promote methylation is controversial.

My laboratory’s recent work with DDM1 – an ancient protein conserved between plants and animals that can move nucleosomes – and linker histone H1, which binds to nucleosomes and the intervening ‘linker’ DNA, has allowed us to formulate a model wherein movement of nucleosomes by DDM1 dislodges H1 and allows methyltransferases to access the DNA. Furthermore, this work revealed the existence of unknown factors required to maintain DNA methylation. My laboratory also discovered that DNA methylation influences nucleosome placement, thereby demonstrating that the interaction between DNA methylation and nucleosomes is bidirectional.

My goal is now to deeply understand the connected processes of maintenance methylation and nucleosome placement. This will be achieved through three interconnected research strands: 1) Elucidation of how DNA methylation is maintained within chromatin. 2) Identification of new DNA methylation maintenance factors. 3) Determination of how DNA methylation influences nucleosomes in vivo.

Our ultimate output will be the creation of a mathematical model of DNA methylation maintenance that will incorporate the bidirectional interactions between methylation and nucleosomes. This breakthrough will revolutionize research in the field by permitting the development of precise, quantitative hypotheses about the maintenance and function of DNA methylation within chromatin.

 Publications

year authors and title journal last update
List of publications.
2019 Jaemyung Choi, David B. Lyons, M. Yvonne Kim, Jonathan D. Moore, Daniel Zilberman
DNA Methylation and Histone H1 Jointly Repress Transposable Elements and Aberrant Intragenic Transcripts
published pages: , ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.10.011
Molecular Cell 2019-12-16
2019 Keith D. Harris, James P. B. Lloyd, Katherine Domb, Daniel Zilberman, Assaf Zemach
DNA methylation is maintained with high fidelity in the honey bee germline and exhibits global non-functional fluctuations during somatic development
published pages: , ISSN: 1756-8935, DOI: 10.1186/s13072-019-0307-4
Epigenetics & Chromatin 12/1 2019-12-16
2017 David B Lyons, Daniel Zilberman
DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.30674
eLife 6 2019-05-15
2017 Daniel Zilberman
An evolutionary case for functional gene body methylation in plants and animals
published pages: , ISSN: 1474-760X, DOI: 10.1186/s13059-017-1230-2
Genome Biology 18/1 2019-05-15

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