CORDIS
EU research results

CORDIS

English EN

"DNA methylation, hydroxymethylation and cancer"

Objective

"DNA methylation patterns are frequently perturbed in human diseases such as imprinting disorders and cancer. In cancer increased aberrant DNA methylation is believed to work as a silencing mechanism for tumor suppressor genes such as INK4A, RB1 and MLH1. The high frequency of abnormal DNA methylation found in cancer might be due to the inactivation of a proofreading and/or fidelity system regulating the correct patterns of DNA methylation. Currently we have very limited knowledge about such mechanisms.

In this research proposal, we will focus on elucidating the biological function of a novel protein family, which catalyzes the conversion of 5-methyl-cytosine (5-mC) to 5-hydroxymethyl cytosine (5-hmC). By catalyzing this reaction the TET proteins most likely work as DNA demethylases, and they might therefore have a role in regulating DNA methylation fidelity. Interestingly, accumulated data has in the last 2 years shown that TET2 is one of the most frequently mutated genes in various hematological cancers. We propose to investigate the molecular mechanisms by which TET2 regulates normal hematopoiesis, how its inactivation leads to hematopoietic malignancies and how the protein contributes to the regulation of DNA methylation patterns and transcription. Furthermore, we propose several experimental approaches for identifying proteins required for the recruitment of TET proteins to target genes and to analyze their role in the regulation of DNA methylation patterns and in cancer. Finally, we will investigate the potential functional role of 5-hmC and explore the potential mechanisms by which this modification could be erased.

We expect to provide new insights into the biology of DNA methylation, hydroxymethylation and contribute to unravel the roles of TET proteins in normal physiology and cancer."
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Principal Investigator

Kristian Helin (Prof.)

Host institution

KOBENHAVNS UNIVERSITET

Address

Norregade 10
1165 Kobenhavn

Denmark

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 2 298 000

Principal Investigator

Kristian Helin (Prof.)

Administrative Contact

Ivan Kristoffersen (Mr.)

Beneficiaries (1)

Sort alphabetically

Sort by EU Contribution

Expand all

KOBENHAVNS UNIVERSITET

Denmark

EU Contribution

€ 2 298 000

Project information

Grant agreement ID: 294666

Status

Closed project

  • Start date

    1 July 2012

  • End date

    30 June 2017

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 2 298 000

  • EU contribution

    € 2 298 000

Hosted by:

KOBENHAVNS UNIVERSITET

Denmark