Functional analysis of transposable elements

Almost all the cells of the human body contain the same DNA, and thus the same set of genes. Nevertheless, they are able to develop different structures and functions. This is because not all genes are turned on or expressed in a given cell. The subset of genes that are expressed in each cell is controlled by a process known as gene regulation. Instructions determining when, where, and how strongly a gene will be expressed are encoded by DNA sequences called cis-regulatory elements. These sequences are recognized and bound by transcription factor proteins. Transcription factor proteins act as master switches, turning genes on and off. Cis-regulatory elements and genes are hidden within a high-order structure, the chromatin, consisting of the DNA wrapped around histone proteins. The chromatin packs the DNA into a volume small enough to fit into the cell nucleus. For the cells machinery to express the genes, the chromatin must first be unfolded. Chromatin folding and unfolding is associated with the addition of chemical tags or epigenetic marks to specific positions of the DNA or the histones. Combinations of epigenetic marks are assumed to determine the role of cis-regulatory elements in turning genes on and off. Epigenetic marks have been the study focus of several international research projects. Thus, the Encyclopedia of DNA Elements (ENCODE) has catalogued the epigenetic marks observed in different cell types using methods such as chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq). Even if the approach has proven fruitful, the analysis of the data generated by ChIP-seq is challenging for repetitive DNA sequences. And unfortunately, approximately two thirds of the DNA in a human cell comprises sequences that are present in multiple copies. Many of such sequences are transposable elements or jumping genes, i.e., DNA sequences that can move (jump) or introduce copies of themselves into a different location of the DNA. Although transposable elements were once written off as junk, they are now appreciated for their functional roles in a variety of biological phenomena. Unfortunately, the repetitive nature of transposable elements makes them not amenable to standard bioinformatics tools. For this reason, and despite considerable research in the last few years, our knowledge of transposable elements remains limited. By developing a new bioinformatics approach that aims at characterizing groups of similar transposable elements rather than individual transposable elements this project is set to identify transposable elements with cis-regulatory function.

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