Signals are transmitted to chromatin to facilitate rapid, robust, and selective gene expression within the three billion base-pair genome in response to environmental cues, such as pathogen sensing. The goal of our ongoing research is to reveal mechanisms allowing for this scope and selectivity, and to understand them in the context of dynamic and fluid chromatin and all of its constituents (as a multi-molecular assembly or “biomolecular condensate”). Our recent studies of pathways that transmit extracellular signals to selectively induce gene expression establish the cooperative function of epigenetic mechanisms (histone modifications) and transcription factor activation and their coordinated regulation by chromatin-associated kinases. We are finding that these signaling-to-chromatin pathways are potent in regulation of enhancer activation and higher order chromatin architecture, both during the inflammatory process and in cancer. In ongoing and future work we extend these studies to understand how epigenetic processes provide an “evolutionary toolbox” for adaptations driven by spatiotemporal changes in gene expression. These studies have potential to synthesize an understanding of the extensive cooption of immune genes for non-immune processes (ex. thermogenesis, neuronal development), reveal novel mechanisms of adaptation, and explain inflammation- and age-associated pathologies.
- Signaling to chromatin for dynamic regulation of chromatin architecture and transcription
- Function of chromatin associated kinases in inflammation and cancer
- Epigenetic "scars" of chronic inflammation and accelerated aging in chronic HIV infection