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The role of E6/E7 HPV16 oncogenes in chromatin remodelling through components of NuRD complex (MBD2, MBD3)

Project Code: PN-II-RU-TE-2014-4-2502

Programme: Human Resources- Research projects to stimulate the establishment of young independent research teams - TE
Financier: UEFISCDI

Project duration: 24 months (October 2015 – September 2017)

Coordinating Institution: Stefan S. Nicolau Institute of Virology (www.virology.ro)
Address: 285Mihai Bravu Ave., sector 3, Bucharest, Romania; tel/fax: 021 3242590

Project Manager: Dr. BOTEZATU ANCA, CSIII
e-mail: gnanka30 @ yahoo.com
Research Team: Dr. Botezatu Anca CSIII, Dr. Adriana Plesa CSIII, Dr. Iancu Iulia Virginia CS,

Total Budget: 550.000 lei



Cervical cancer is the third most commonly diagnosed type of cancer and one of the most frequently occurring malignant tumors in women worldwide. Human papilloma virus (HPV) is considered the etiologic agent of cervical neoplasia. The transforming potential of high risk human papillomavirus (hrHPV) is due to E6 and E7 viral oncoproteins. Persistent hrHPV infection leads to changes in the host genome and epigenome. The control of gene expression is complex and involves epigenetic changes (DNA methylation, histone modification, miRNAs activity). The nucleosome remodeling and deacetylation complex (NuRD) is a group of associated proteins with ATP-dependent chromatin remodeling and histone deacetylase activities. MBD2 and MBD3 proteins from NuRD complex exhibit methyl-CpG-binding domains (MBD), which mediate an interaction with methylated DNA. At molecular level, MBD2 binds to methylated DNA (at 5-methylcytosine -5 mC), while MBD3 binds to DNA at 5-hydroxymethylcytosine (5 hmC). Given the increasing data regarding the MBD2 and MBD3 functional differences and similarities, the proposal aims to assess the viral oncogenes influence on the MBDs overall binding pattern to CpG islands from promoters, gene control region, enhancers, gene bodies. The resulting data will help to elucidate the mechanisms leading to oncogenesis and to identify new potential therapeutic targets.


Concrete objectives of the project

Phase I  (2015.20.01 - 2015.12.30)

Phase II   (2016.01.01  -  2016.12.30)