Abstract：
:Two decades of research identified more than a dozen clock genes and defined a biochemical feedback mechanism of circadian oscillator function. To identify additional clock genes and modifiers, we conducted a genome-wide small interfering RNA screen in a human cellular clock model. Knockdown of nearly 1000 genes reduced rhythm amplitude. Potent effects on period length or increased amplitude were less frequent; we found hundreds of these and confirmed them in secondary screens. Characterization of a subset of these genes demonstrated a dosage-dependent effect on oscillator function. Protein interaction network analysis showed that dozens of gene products directly or indirectly associate with known clock components. Pathway analysis revealed these genes are overrepresented for components of insulin and hedgehog signaling, the cell cycle, and the folate metabolism. Coupled with data showing many of these pathways are clock regulated, we conclude the clock is interconnected with many aspects of cellular function.
journal_name
Celljournal_title
Cellauthors
Zhang EE,Liu AC,Hirota T,Miraglia LJ,Welch G,Pongsawakul PY,Liu X,Atwood A,Huss JW 3rd,Janes J,Su AI,Hogenesch JB,Kay SAdoi
10.1016/j.cell.2009.08.031subject
Has Abstractpub_date
2009-10-02 00:00:00pages
199-210issue
1eissn
0092-8674issn
1097-4172pii
S0092-8674(09)01099-Xjournal_volume
139pub_type
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