Despite recent progress, our knowledge of JAK-STAT biology remains essentially one-dimensional: the mechanisms of signal integration and the changes to chromatin architecture driven by JAKs and STATs under different conditions are only beginning to emerge. JAK-STAT signalling components are known to interact with “chromatin modifiers”. To advance research into the molecular mechanisms linking JAK-STAT signaling with chromatin landscapes we expect an integrated analysis will uncover at least the following concrete results in the initial four years. These are important milestones on the path to a comprehensive model of how JAK-STAT regulates chromatin, which will be achieved in the future:
Hotspots of chromatin dynamics: We will compile a comprehensive catalogue of genomic regions that change their epigenomic state in response to JAK-STAT signalling during normal development and/or in disease.
Correlation of JAK-STAT dependent epigenome signals: The consistent and standardized quantification of different epigenome signals will enable computational modelling of the effects of JAK-STAT signalling on the epigenomic landscape.
Regulatory networks encoded in chromatin: Exploiting transcription factor footprints encoded in the chromatin accessibility data, we will explore transcription factor footprints and regulatory networks involved in JAK-STAT-dependent regulation of chromatin
Database of JAK-STAT epigenomics: The integrated resource that we will create in this SFB will provide an important reference for the wider research community.