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Speaker: William J. Belden, Associate Professor Dept of Animal Sciences, Rutgers University New Brunswick, NJ
Title: The Circadian Clock, Heterochromatin, Long non-coding RNAs and Antibody Single-chain Variable Fragments
Abstract: Circadian rhythm is generated by transcriptional negative feedback loops and require histone modifications and chromatin remodeling to ensure appropriate timing and amplitude of clock gene expression. Circadian modifications to histones mediate transcriptional initiation and feedback inhibition serving as signaling platform for chromatinremodeling enzymes. There is a conserved mechanism of circadian-regulated facultative heterochromatin (CRFH) at clock genes in Neurospora, Drosophila, and mice that consists of anti-phasic rhythms in activating and repressive modifications that cycle between transcriptionally permissive and non-permissive. During feedback repression, a rhythm in histone H3 lysine 9 methylation (H3K9me) and heterochromatin protein 1 (HP1) occurs at the central clock genes and at telomeres. In Neurospora, the rhythm in facultative heterochromatin is mediated by the frequency (frq) natural antisense transcript (NAT) qrf while telomeric heterochromatin appears to involve the lncRNA TERRA. In Neurospora H3K9me3 requires H3K4me3 and there are H3K4me3:H3K9me3 bivalent domains. We’ve embarked on making single-chain variable fragments (scFv) to use as competitive inhibitors of bivalent chromatin to better understand their function in development.