Polycomb; CpG island; functional genomics; transcription factor; chromatin; gene regulation; stem cells
Colombo Daniele F, Burger Lukas, Baubec Tuncay, Schübeler Dirk (2017), Binding of high mobility group A proteins to the mammalian genome occurs as a function of AT-content, in PLOS Genetics
, 13(12), e1007102-e1007102.
Hartl D, Krebs AR, Jüttner J, Roska B, Schübeler D (2017), Cis-regulatory landscapes of four cell types of the retina, in Nucleic Acids Resr
, 45((29)), 11607-11624.
Krebs Arnaud R., Imanci Dilek, Hoerner Leslie, Gaidatzis Dimos, Burger Lukas, Schübeler Dirk (2017), Genome-wide Single-Molecule Footprinting Reveals High RNA Polymerase II Turnover at Paused Promoters, in Molecular Cell
, 67(3), 411-422.e4.
Precise regulation of gene expression underlies multicellularity. The vast majority of initiation events of RNA polymerase II in the mouse and human genome occur at CG rich promoters, so called CpG islands (CGI). This class of regulatory elements provides a central hub for proximal gene regulation in mammals where key activating and repressing signals converge. Nevertheless, it remains to be investigated if and how their CG density is involved in their genetic and epigenetic regulation. Here we propose to use novel tools of quantitative genomics to study comprehensively the constituents that act in cis and in trans to activate CGI promoters. In addition we will ask how the Polycomb system is targeted to CGI promoters and how it functions in their transient repression.Through genomic mapping and genetic deletion we will determine binding and function of DNA and chromatin binding factors involved in regulating CGIs. In order to systematically test the regulatory logic of CGIs we will establish a high throughput reporter assay enabling us to quantify the transcriptional activity of thousands of synthesized promoter haplotypes at a defined chromosomal locus. This will help to decode the regulation of CGIs and to better understand how natural sequence variation influences their activity. Together this integrative project will apply new genome editing and genomics approaches to shed light on an important class of regulatory regions in mammalian genomes.