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.
Maintenance of circadian rhythms is essential to many aspects of human health, including metabolism and neurological and psychiatric well-being. Although the importance of daily cycling of gene expression has been well established, much work remains to be done to describe the individual components of this system. This proposal aims to identify the transcriptional network regulated by a core circadian transcription factor, CLOCK, in human neocortex and to characterize its role in brain evolution and mental health.
| Fontenot, Miles R; Berto, Stefano; Liu, Yuxiang et al. (2017) Novel transcriptional networks regulated by CLOCK in human neurons. Genes Dev 31:2121-2135 |
