Howard Hughes Medical Institute Professor; Arts and Sciences Distinguished Professor, Department of Biology Emory University
Mechanisms of Transgenerational Inheritance of Obesity Epiphenotypes
The goal of our research is to understand epigenetic mechanisms controlling the expression of eukaryotic genes. We are interested in the role of the primary structure of the chromatin fiber, as determined by histone tail modification, in the regulation of transcription. In particular, we have found that phosphorylation of hitone H3 is an essential step during the promoter clearance process in the transcription of all Drosophila genes. The levels of phosphorylated histone H3 are maintained by a balance between the activities of the JIL-1 kinase and the PP2A protein phosphatase. We are currently exploring the mechanisms by which the activity of these two enzymes is regulated to control chromatin structure and transcription. A second focus of our lab is to study the organization of the chromatin fiber within the eukaryotic nucleus and the mechanisms controlling this arrangement, with the idea that nuclear organization carries epigenetic information. Sequences involved in the establishment and/or maintenance of nuclear organization are called chromatin insulators. We have identified several different proteins that form a complex with insulator DNA and we are in the process of analyzing their function. The working hypothesis we are currently testing is that insulators are responsible for controlling patterns of nuclear organization required for cell differentiation. Alterations in insulator function that disrupt this organization could lead to cancer and other diseases.