Análise epigenética do gene SOCS1 e sua associação com a periodontite crônica

Author(s)

Aline Cristiane Planello

• Document type: Doctoral Thesis
• Press: Piracicaba, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba
• Defense date: 2014-02-21

Examining board members

Ana Paula de Souza; Paula Cristina Trevilatto; Raphael Bessa Parmigiani; Daniel Diniz de Carvalho; Ricardo Della Coletta

• Advisor: Ana Paula de Souza

Abstract

Chronic inflammation is known to induce epigenetic alterations, in particular alterations in DNA methylation. SOCS1 CpG island (CGI) has been demonstrated hypermethylated in many types of cancer and inflammation-associated diseases. However, little is known about the epigenetic changes associated with chronic periodontitis. In order to address this question, we investigated DNA methylation of oxon 2 of SOCS1 CGI and its functional relevance to chronic periodontitis in 90 gingival tissue samples using methylation sensitive high resolution melting (MS-HRM). We found this region to be hypermethylated when compared with healthy controls. No changes in gene expression were observed. Further investigations of SOCS1 sequence showed enhancer marker at SOCS1 region. Correlation analysis of Dnase I hypersensitivity site (DHS), which is associated with regulatory region, showed a DHS inside exon2 SOCS1 correlated with several promoter in the neighboring region, considered target genes. Fragments harboring the SOCS1 region found to be differentially methylated, were cloned into a CpG free-Luc reporter vector just upstream the promoter. Unmethylated and methylated fragments were tested. The unmethyalted fragment enhanced the promoter activity of the promoter. Strikingly, not only the exon2 of SOCS1 CGI presented enhancer activity but also it had its activity disrupted by DNA methylation. Accordingly, negative correlation between SOCS1 methylation and expression of neighboring genes was observed in chronic inflammation. The data indicate that the primary function of enhancer DNA methylation is to control its regulatory function and the transcription levels of enhancer target genes, which can be evidenced by exon 2 SOCS1 CGI hypermethylation on chronic inflammation (AU)

• FAPESP's process: 10/05151-9 - DNA methylation analysis of SOCS1, SOCS2 and SOCS3 gene promoters in oral epithelial cells and gingival tissue cells from individuals with chronic periodontitis: association with gene transcription
• Grantee: Aline Cristiane Planello
• Support Opportunities: Scholarships in Brazil - Doctorate