Role of BEN domain proteins in chromatin organization and gene expression

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Accurate control of gene expression is crucial for cell survival and is clearly dependent on the chromatin state. Chromatin consists of DNA plus histone proteins that wrap the DNA into a more compact structure. The chromatin structure can be modified in many ways to target specific protein binding, alter gene expression, or initiate DNA replication. The project will determine how a particular protein alters chromatin organization and transcription within the eukaryotic genome. This interdisciplinary project has a strong outreach component and will engage undergraduate students in research, which will include high-resolution microscopy as well as time-lapse live cell imaging. This project will include undergraduate women and minority students in the research project; provide opportunities for community college students via research internships; and support a workshop and symposium on live cell imaging. Exposing young and bright students to research early on will be highly beneficial and instill in them a sense of scientific awareness and potential. The function of a protein can often be predicted by the presence of domains that are either distinct functional or structural units. These domains can promote binding to specific proteins or nucleic acids. The BEN-domain is a protein domain that is present in diverse proteins in metazoans as well as in viruses. It is predicted to mediate protein-DNA and protein-protein interactions to regulate chromatin organization and transcription. BEN domain-containing proteins are emerging rapidly as an important class of proteins involved in gene regulation. Several BEN-containing proteins including BANP/SMAR1, Mdg4, BEND have chromatin-related functions and regulate gene expression. However, the molecular basis of how the BEN-domain containing gene family regulates chromatin function and transcription remains to be established. The objective of the project is to dissect the molecular basis of transcription repression by the quadruple BEN-domain containing protein BEND3 and determine its physiological role in mammalian cells. The PIs laboratory utilizes state-of the art cell biological approaches including time-lapse imaging, super-resolution structural illumination imaging and combines these observations with biochemical approaches. This project is relevant to the NSF mission and will further the understanding of a basic biology question: how chromatin organization dictates transcriptional regulation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.