Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: An integrative approach using high-throughput datasets

M. S. Vijayabaskar, Debbie K. Goode, Nadine Obier, Monika Lichtinger, Amber M. L. Emmett, Fatin N. Zainul Abidin, Nisar Shar, Rebecca Hannah, Salam A. Assi, Michael Lie-A.-Ling, Berthold Göttgens, Georges Lacaud, Valerie Kouskoff, Constanze Bonifer, David R. Westhead

Abstract: Author summary The inherited information in our DNA genomes is a code which defines both the functional units (proteins, nucleic acids etc.), and patterns of their usage, necessary to make life. The genome in mammals, such as man and mouse, has genes which code for about 20000 different proteins, but the usage of these proteins differs in each different type of cell within these complex multicellular organisms. How this differential usage is controlled in known as genetic regulation, and that is what we study here. We know that the details lie in how genes are turned on and off, but until the advent of high-throughput sequencing technology a genome-wide study was nearly impossible. Further complicating our efforts to understand genetic regulation is the involvement of parts of the genome that were previously deemed junk. In this work, we have focussed on how the genes are controlled at various developmental stages in mouse, by looking at the sequencing data from different regulatory mechanisms such as protein binding and local changes to DNA packaging etc. On a gene-by-gene basis, we have built statistical models that predict how genes are controlled when cells develop. These predictions provide a focus for future experimental studies of genetic regulation.