Neocortical regulation of circadian rhythms

Ut Southwestern Medical Center, Dallas TX

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Abstract

? DESCRIPTION (provided by applicant): For the past 20 years, the molecular mechanisms underlying circadian rhythm and its relevance to human health have been the subject of intense research. The transcription factor CLOCK is a key driver of circadian cycling. Although genome-wide transcriptomic profiling studies have focused on cyclical gene expression in the liver and the suprachiasmatic nucleus, little is known about the function of CLOCK in other areas of the central nervous system. We have previously shown that CLOCK is more highly expressed in human neocortex compared to non-human primates, raising questions concerning the role of CLOCK in human brain evolution and its relevance to human mental health. I hypothesize that neocortical expression of CLOCK in the human brain is critical for regulating novel transcriptional networks. To test this hypothesis, we propose to identify the transcriptional network regulated by CLOCK in human neocortex through RNA- and ChIP-seq.