RESEARCH SUMMARY

Epigenetics has become a fundamental discipline in the study of genome biology. Cell growth and differentiation is largely regulated by epigenetic processes. The alteration of these epigenetic mechanisms is associated with numerous pathologies, notably cancer.

One of the best- known epigenetic modifications is DNA methylation. DNA methylation occurs in cytosines that precede guanines ( CpG dinucleotides). CpGs are not randomly distributed in the human genome, instead there are CpG-rich regions, known as CpG islands, which span the 5’ end of the regulatory region of many genes. These CpG islands are usually not methylated in normal cells but become aberrantly hypermethylated in cancer. When DNA hypermethylation occurs at tumor suppressor genes it can cause their inactivation and, consequently, their protective role against tumor development is lost. Although locus-specific DNA demethylation also exits, its role in tumorigenesis is still poorly understood.

In addition to DNA methylation, another important epigenetic mechanism involved in chromatin regulation, including gene expression control, is the reversible chemical modification of the amino-terminal tail of histones. Histone modifications include lysine and arginine acetylation, lysine methylation, serine fosforilation and lysine ubiquitination mediated by histone acetyl transferases (HATs), histone methyl transferases (HMTs), histone desacetylases (HDACs), and histone demethylases (HDMs) among other enzymes. The combination of the different histone modifications could play an important role in regulating chromatin function. Along with other researchers we have shown that histone posttranslational modifications are also frequently altered in cancer.

Currently, our research focuses on the study of locus-specific and genome-wide epigenetic mechanisms such as DNA methylation and histone post-translational modifications during cell differentiation, and their alterations in cancer and aging. We are particularly interested in the role of locus-specific DNA demethylation in health and disease and we are involved in ultra-deep sequencing projects to characterize the genome-wide patterns of specific epigenetic marks in human tumorigenesis.

In addition to standard techniques of molecular biology and cell culture we routinely work with the following specific epigenetic techniques: bisulfite pyrosequencing and bisulfite sequencing of multiple clones, chromatin immunoprecipitation (ChiP), ChiP-on-qPCR, ChiP-on-ChiP, ChiP-on-seq and HPLC, HPCE and mass spectrometry analysis of global DNA methylation and histone post-translational modifications.