Luca Pinello, Dana Faber Cancer Research Center and Harvard University, USA

Epigenetic plasticity: why DNA sequence matters
In this tutorial we present the basic concepts of the Epigenetics, which tries to answer to a fundamental question:  how do the many cell types of the body maintain drastically different gene expression patterns while sharing exactly the same DNA?

In the last years distinct epigenetic changes have been identified across developmental stages, between different cell-types, or associated with various diseases, which explain, at least in part, why gene activities are regulated differently in different cell-types despite sharing the same genome. However, the underlying mechanisms that regulate cell-type dependent epigenetic changes are still poorly understood. While the DNA sequence cannot predict cell-type specific changes, it can demarcate regions with distinct variability and is highly associated with tissue-related plasticity.

We then present some computational methods that can predict genome-wide patterns of epigenetic patterns using sequence features such as periodicity and word frequencies. Using these methods we found that a significant amount of genome-wide epigenomic marks variations (such as methylation and acetylation) can be explained by the DNA sequenques. Moreover, we also found that the level of specificity associated with H3K4me1 target sequences is highly cell-type specific and
highest in embryonic stem (ES) cells.

References