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Series GSE4245

Query DataSets for GSE4245

Status

Public on Jun 21, 2006

Title

EGF treated SCN versus intra-animal control at two circadian times

Platform organism

Rattus norvegicus

Sample organisms

Rattus norvegicus; synthetic construct

Experiment type

Expression profiling by array

Summary

Background:

Identifying the gene regulatory networks governing physiological signal integration remains an important challenge in circadian biology. Epidermal growth factor receptor (EGFR) has been implicated in circadian function and EGFR is expressed in the suprachiasmatic nucleus (SCN), the core circadian pacemaker. The transcription networks downstream of EGFR in the SCN are unknown, but by analogy to other SCN inputs we expect the response to EGFR activation to depend on circadian timing and thus be “circadian context–dependent”.

Results:
We have undertaken a systems level analysis of EGFR circadian context–dependent signaling in the SCN. We collected gene expression profiles to study how the SCN response to EGFR activation depends on circadian timing. Mixed–model analysis of variance (ANOVA) was employed to identify genes with circadian context–dependent EGFR regulation. The expression data was integrated with transcription factor (TF) binding predictions through gene group enrichment analyses to generate robust hypotheses about TFs responsible for the circadian phase–dependent EGFR responses.

Conclusions:
The analysis results suggest that the transcriptional response to EGFR signaling in the SCN may be partly mediated by established EGFR signaling regulated TFs (AP1, Ets1), TFs involved in circadian clock entrainment (CREB), and by core clock TFs (Rorα). qRT-PCR measurements of several TF expression levels support a model in which circadian context-dependent EGFR responses are partly achieved by circadian regulation of upstream signaling components. Our study suggests an important role for EGFR signaling in SCN function and provides an example for gaining physiological insights through systems-level analysis.
Keywords: dose response; repeat sample

Overall design

A 2X2 factorial experimental design was used to investigate differences between "day" (8 hours after lights on) and "night" (2 hours after lights off) SCN gene expression responses to EGFR activation induced by EGF treatment (20 nM, 1 hr).

Two SCN were obtained from each rat and served as EGF–treated and vehicle-treated samples. Pairing control and treated samples from the same rat permitted detection of EGF effects in the presence of substantial animal-to-animal variability. SCN from two rats were experimentally treated at each circadian time, yielding a total of eight biological samples. Since our goal was a preliminary characterization of EGFR response clock phase dependency, samples were hybridized to one microarray each. A universal reference design was used for the microarrays themselves.

Contributor(s)

Zak DE, Hao H, Vadigepalli R, Miller GM, Ogunnaike BA, Schwaber JS

Citation(s)

16784547

Submission date

Feb 15, 2006

Last update date

Mar 16, 2012

Contact name

Gregory Miller

E-mail(s)

miller@che.udel.edu