Gene regulation in chromatin

Individual cell types are defined by the particular set of genes they express. How does the cell organize the genome to activate the right gene when needed and to keep it silent at other times? In eukaryotes this regulation relies on a complex interplay between proteins that bind to regulatory sequences and the packaging of DNA, which can be changed by modifying proteins within nucleosomes (histones) or by methylating the DNA without changing its sequence. These epigenetic modifications provide an additional layer of information that in concert with the genetic sequence regulate genome activity. We are using mammalian stem cell models to ask how chromatin structure and DNA methylation are regulated by the underlying DNA sequence and how they crosstalk to transcription. Towards this goal we combine molecular biology and functional genomic approaches. This enables us to monitor the epigenome and its dynamics in an unbiased way and to generate regulatory models from genome-wide datasets, which we test in cellular models by genetic perturbation and gene targeting approaches.
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