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MaintainMeth SIGNED

Quantitative analysis of DNA methylation maintenance within chromatin

Total Cost €

EC-Contrib. €

Partnership

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MaintainMeth project word cloud

Explore the words cloud of the MaintainMeth project. It provides you a very rough idea of what is the project "MaintainMeth" about.

linker dislodges discovered formulate cytosine function binds controversial interaction reproduction animal allowed elucidation expression influences bidirectional unknown nucleosomal maintenance creation revolutionize interactions enzymes accurate modification breakthrough ddm1 understand regulate move demonstrating nucleosomes quantitative human h1 chemical incorporate conserved histone methylation interconnected permitting plant intervening animals hinder output replicated deeply laboratory vivo copied model maintained identification nucleosome connected chromatin proteins strands ultimate patterns revealed ancient precisely plants dna protein health existence mathematical thereby methyltransferases contend precise complexes hypotheses tight placement gene movement

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 title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
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 JOHN INNES CENTRE Organization address address: NORWICH RESEARCH PARK COLNEY city: NORWICH postcode: NR4 7UH website: www.jic.bbsrc.ac.uk contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	UK (NORWICH)	coordinator	2˙749˙962.00

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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

List of publications.
year	authors and title	journal	last update
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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