Analysis of circadian pattern reveals tissue-specific alternative transcription in leptin signaling pathway.
BACKGROUND
It has been previously reported that most mammalian genes display a circadian oscillation in their baseline expression. Consequently, the phase and amplitude of each component of a signal transduction cascade has downstream consequences.


RESULTS
Here, we report our analysis of alternative transcripts in the leptin signaling pathway which is responsible for the systemic regulation of macronutrient storage and energy balance. We focused on the circadian expression pattern of a critical component of the leptin signaling system, suppressor of cytokine signaling 3 (SOCS3). On an Affymetrix GeneChip 430A2 microarray, this gene is represented by three probe sets targeting different regions within the 3' end of the last exon. We demonstrate that in murine brown adipose tissue two downstream 3' probe sets experience circadian baseline oscillation in counter-phase to the upstream probe set. Such differences in expression patterns are a telltale sign of alternative splicing within the last exon of SOCS3. In contrast, all three probe sets oscillated in a common phase in murine liver and white adipose tissue. This suggests that the regulation of SOCS3 expression in brown fat is tissue specific. Another component of the signaling pathway, Janus kinase (JAK), is directly regulated by SOCS and has alternative transcript probe sets oscillating in counter-phase in a white adipose tissue specific manner.


CONCLUSIONS
We hypothesize that differential oscillation of alternative transcripts may provide a mechanism to maintain steady levels of expression in spite of circadian baseline variation.
Ptitsyn
Andrey A
AA
Experimental Obesity Laboratory, Louisiana State University Pennington Biomedical Research Center, 6400 Perkins Rd, Baton Rouge, LA 70808, USA. Andrey.Ptitsyn@colostate.edu
Gimble
Jeffrey M
JM
D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D020738:Leptin / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009991:Oscillometry / Q000379:methods; D010363:Pattern Recognition, Automated / Q000379:methods; D015398:Signal Transduction / Q000502:physiology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology*
D020738:Leptin; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors