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TET2rec SIGNED

Mechanisms of TET2 DNA demethylase recruitment to specific genomic regions

Total Cost €

EC-Contrib. €

Partnership

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TET2rec project word cloud

Explore the words cloud of the TET2rec project. It provides you a very rough idea of what is the project "TET2rec" about.

eleven chip hypothesize epigenetic lack yield previously followed identity understand proteins missense inspect translocation seek unveil genome cxxc involvement goals mechanisms wildtype domain chromatin evolution reversible deregulated human frequently region spectrometry tet2 specification cancer tet dioxygenase myeloid structural tet1 modification altogether mutations immunoprecipitation aml found homologues methylcytosine roles mammals sequencing leukemia motif binds hence share terminal recruitment interacting demethylase mass experiments demethylation significantly normal cells cellular recruited first functional ten discovered methylation lost function interact truncated perform mutated tet3 patients participate mediate binding dna acute exerts

Project "TET2rec" data sheet

The following table provides information about the project.

Coordinator	KOBENHAVNS UNIVERSITET Organization address address: NORREGADE 10 city: KOBENHAVN postcode: 1165 website: www.ku.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	200˙194 €
EC max contribution	200˙194 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2017
Funding Scheme	MSCA-IF-EF-ST
Starting year	2018
Duration (year-month-day)	from 2018-03-01 to 2020-02-29

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	KOBENHAVNS UNIVERSITET KOBENHAVNS UNIVERSITET Organization address address: NORREGADE 10 city: KOBENHAVN postcode: 1165 website: www.ku.dk contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DK (KOBENHAVN)	coordinator	200˙194.00

Map

Project objective

TET2 (Tet Methylcytosine Dioxygenase 2) is a DNA demethylase frequently mutated in patients with Acute Myeloid Leukemia (AML). DNA methylation is an epigenetic modification with key roles in the specification of cellular identity, and, when deregulated, in cancer. DNA methylation is a reversible process and, only recently, it was discovered that TET (Ten-eleven Translocation) proteins mediate DNA demethylation. Mammals have three TET homologues (TET1-3). While TET1 and TET3 share an N-terminal DNA-binding domain (CXXC motif), TET2 has lost its CXXC motif during evolution. Therefore, it is not understood how TET2 binds DNA. Due to the lack of a known DNA-binding domain in TET2, I hypothesize that TET2 may require to interact with proteins to be recruited to DNA, which is essential for its function. Hence, the main goal of my proposal is to understand how TET2 binds to DNA and to identify interacting proteins that participate in this recruitment. I also aim to unveil whether cancer-associated mutations affect TET2 recruitment. To achieve these goals, I will perform a structural-functional analysis of TET2. First, I will perform Chromatin Immunoprecipitation (ChIP) followed by whole genome sequencing of wildtype and truncated TET2. Thus, I will identify the region(s) required for the binding of TET2 to DNA. Next, I will seek proteins that interact with TET2 through the previously identified region by Mass Spectrometry and I will test their involvement in TET2 recruitment to DNA. Furthermore, I will perform similar experiments to inspect the impact of TET2 missense mutations found in human cancer on TET2 recruitment to DNA. Altogether, this project will yield a better understanding of how TET2 is recruited to DNA. The results obtained will significantly impact the epigenetic field and allow for a better understanding of the mechanisms by which TET2 exerts its function in normal cells and how TET2 mutations contribute to cancer.

Publications

List of publications.
year	authors and title	journal	last update
2019	Kasper D. Rasmussen, Ivan Berest, Sandra KeÎ²ler, Koutarou Nishimura, LucÃa SimÃ³n-Carrasco, George S. Vassiliou, Marianne T. Pedersen, Jesper Christensen, Judith B. Zaugg, Kristian Helin TET2 binding to enhancers facilitates transcription factor recruitment in hematopoietic cells published pages: 564-575, ISSN: 1088-9051, DOI: 10.1101/gr.239277.118	Genome Research 29/4	2020-02-05

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The information about "TET2REC" are provided by the European Opendata Portal: CORDIS opendata.