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.
(2) MOUSE MODELS FOR FUNCTIONAL HISTONE GENETICS
Despite widely held assumptions and abundant descriptive data, we lack an understanding of the function of histone modifications in complex organisms, i.e. deuterostomes, vertebrates. This is due to the experimental intractability of histone genetic complexity. A motivating challenge for the lab has been to address this fundamental gap in the field of epigenetics, which is central to understanding how large genomes in complex organisms are regulated to direct cellular differentiation and rapid environmental responses across physiologic systems and their dysregulation in disease. We are building a platform for functional histone studies in mammalian systems. With these approaches, we set out to address fundamental questions: What are the roles of histones and their modification in mammalian cell differentiation in vivo? Do individual histone residues and their modification have cell type-specific effects, instruct cell fate, or direct malignancy? Are some essential for all cell types?