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Evaluation of post-translational modifications of histones in colorectal tumor cell lines with different patterns of DNA methylation

Grant number: 13/08330-0
Support type:Scholarships in Brazil - Master
Effective date (Start): November 01, 2013
Effective date (End): May 31, 2015
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Raphael Bessa Parmigiani
Grantee:Nayara Trevisan dos Santos Doimo
Home Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil

Abstract

The colorectal cancer (CRC) is one of the most common malignant neoplasm diagnosticated in the world. The CRC was considered a predominantly genetic disease, characterized by the accumulation of genetic changes that confer proliferative advantages to a particular cell clone. However, subsequent studies showed that epigenetic mechanisms may also be deregulated in tumor and lead to its formation. The importance of the role of epigenetic alterations in the pathogenesis of CRC was confirmed by the identification of CpG islands methylator phenotype (CIMP), characterized by the high frequency of methylation in different regions of the genome, and identified in 20-30% of CRC samples. Considering that DNA methylation is modulated coordinately with other epigenetic changes, it can be inferred that in addition to this mechanism, the tumors with this phenotype also exhibit other deregulated epigenetic processes. The histone modifications, for example, may also contribute to the formation and evolution of tumors due to its role in the regulation of genes which are involved in different cellular processes, such as transcription, replication and DNA repair. Although DNA methylation has been extensively studied in CRC samples, the same did not occur about the histone modifications. Thus, this study aims to characterize the profile of histone modifications in colorectal tumor cell lines and correlate it with different subgroups of CIMP. This characterization will be performed using the technique of chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq). Thereby, it will be possible to uncover differences between histone modifications profiles in cell lines belonging to different subgroups of CIMP. In addition, it will be possible to confirm the important role of other epigenetic modifications, besides DNA methylation, in the development and in the biology of CRC.