A genome-wide RNAi screen for modifiers of the circadian clock in human cells.
Cell
; 139(1): 199-210, 2009 Oct 02.
Article
en En
| MEDLINE
| ID: mdl-19765810
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Relojes Biológicos
/
Ritmo Circadiano
/
Estudio de Asociación del Genoma Completo
Límite:
Humans
Idioma:
En
Revista:
Cell
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos