Assembly of a comprehensive regulatory network for the XXXX circadian clock: a bioinformatics approach.

@entity1 @entity72061 @entity0 @entity10789 @entity4049 @entity5 @entity8713 @entity18962 @entity19829 @entity25933 @entity21121 @entity209 @entity11049
By regulating the timing of cellular processes, the circadian clock provides a way to adapt physiology and behaviour to the geophysical time. In mammals, a light-entrainable master clock located in the @entity10789 ( @entity10789 ) controls peripheral clocks that are present in virtually every body cell. Defective circadian timing is associated with several pathologies such as @entity5 and @entity209 . To better understand the circadian regulation of cellular processes, we developed a bioinformatics pipeline encompassing the analysis of high-throughput data sets and the exploitation of published knowledge by text-mining. We identified 118 novel potential clock-regulated genes and integrated them into an existing high-quality circadian network, generating the to-date most comprehensive network of circadian regulated genes (NCRG). To validate particular elements in our network, we assessed publicly available ChIP-seq data for @entity8713 , REV-ERBa/b and @entity19829 /y proteins and found strong evidence for circadian regulation of @entity11049 , @entity18962 , Dhx6, @entity21121 and @entity72061 all of which are involved in the regulation of tumourigenesis. Furthermore, we identified @entity4049 and @entity25933 , as targets of RORy and REV-ERBa, b, respectively. Most interestingly, these genes were also reported to be involved in miRNA regulation; in particular, @entity4049 regulates several miRNAs, all involved in @entity5 . Thus, @entity4049 represents a novel potential link via which the circadian clock, and specifically RORy, regulates the expression of miRNAs, with particular consequences in @entity0 progression. Our findings bring us one step forward towards a mechanistic understanding of @entity1 circadian regulation, and provide further evidence of the influence of circadian deregulation in @entity5 .
