Abstract

Background DNA methylation is an important epigenetic process that regulates gene expression mainly through its effect on chromatin conformation. It involves the stable maintenance of methylated cytosines at CpG dinucleotides (meCpGs) which in turn can regulate gene expression by two mechanisms: by direct interference with transcription factors binding to their target sequences, or by binding MeCP2 proteins, which recognize methylated DNA and recruit histone deacetilases, resulting in a highly compact chromatin structure. Human Papillomavirus (HPV) E2 protein controls various viral processes, including gene transcription and DNA replication. These activities rely upon its ability to bind as an homodimer to its target sequences (5'-ACCGN4CGGT-3') in the viral DNA. Since these sequences contain CpG dinucleotides, they are potential targets for DNA methylation, and, in fact, it has been demonstrated that E2's ability to bind to its cognate sequence is inhibited by methylation. Different studies have shown that the methylation patterns of HPV DNA, in the long control region (LCR) and the 3' region of the L1 gene, are heterogeneous in human cell lines and clinical samples. The objective of this study was to determine the methylation status of HPV type 18 and 16 DNA in different human-derived cell lines.

Highlights

  • DNA methylation is an important epigenetic process that regulates gene expression mainly through its effect on chromatin conformation. It involves the stable maintenance of methylated cytosines at CpG dinucleotides which in turn can regulate gene expression by two mechanisms: by direct interference with transcription factors binding to their target sequences, or by binding MeCP2 proteins, which recognize methylated DNA and recruit histone deacetilases, resulting in a highly compact chromatin structure

  • DNA methylation patterns observed in three different cell lines containing Human Papillomavirus (HPV) type 18 DNA showed great similarity

  • No methylation of CpG dinucleotides was observed in the complete long control region (LCR) and the 5' region of the E6 gene in CaLo cell line

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Summary

Introduction

DNA methylation is an important epigenetic process that regulates gene expression mainly through its effect on chromatin conformation. It involves the stable maintenance of methylated cytosines at CpG dinucleotides (meCpGs) which in turn can regulate gene expression by two mechanisms: by direct interference with transcription factors binding to their target sequences, or by binding MeCP2 proteins, which recognize methylated DNA and recruit histone deacetilases, resulting in a highly compact chromatin structure. Human Papillomavirus (HPV) E2 protein controls various viral processes, including gene transcription and DNA replication. These activities rely upon its ability to bind as an homodimer to its target sequences (5'-ACCGN4CGGT-3') in the viral DNA. The objective of this study was to determine the methylation status of HPV type 18 and 16 DNA in different human-derived cell lines

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