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Genome-wide expression profiling and bioinformatics analysis of diurnally regulated genes in the mouse prefrontal cortex.

Yang S, Wang K, Valladares O, Hannenhalli S, Bucan M - Genome Biol. (2007)

Bottom Line: The prefrontal cortex is important in regulating sleep and mood.The diurnal expression patterns were confirmed for 16 out of 18 genes in an independent set of RNA samples.The diurnal genes fall into eight temporal categories with distinct functional attributes, as assessed by Gene Ontology classification and analysis of enriched transcription factor binding sites.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics and Penn Center for Bioinformatics, University of Pennsylvania, Philadelphia, PA 19104, USA. shuzhang@mail.med.upenn.edu

ABSTRACT

Background: The prefrontal cortex is important in regulating sleep and mood. Diurnally regulated genes in the prefrontal cortex may be controlled by the circadian system, by sleep:wake states, or by cellular metabolism or environmental responses. Bioinformatics analysis of these genes will provide insights into a wide-range of pathways that are involved in the pathophysiology of sleep disorders and psychiatric disorders with sleep disturbances.

Results: We examined gene expression in the mouse prefrontal cortex at four time points during a 24 hour (12 hour light:12 hour dark) cycle using microarrays, and identified 3,890 transcripts corresponding to 2,927 genes with diurnally regulated expression patterns. We show that 16% of the genes identified in our study are orthologs of identified clock, clock controlled or sleep/wakefulness induced genes in the mouse liver and suprachiasmatic nucleus, rat cortex and cerebellum, or Drosophila head. The diurnal expression patterns were confirmed for 16 out of 18 genes in an independent set of RNA samples. The diurnal genes fall into eight temporal categories with distinct functional attributes, as assessed by Gene Ontology classification and analysis of enriched transcription factor binding sites.

Conclusion: Our analysis demonstrates that approximately 10% of transcripts have diurnally regulated expression patterns in the mouse prefrontal cortex. Functional annotation of these genes will be important for the selection of candidate genes for behavioral mutants in the mouse and for genetic studies of disorders associated with anomalies in the sleep:wake cycle and circadian rhythm.

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Related in: MedlinePlus

A karyotype map showing the chromosome positions and frequencies of diurnally regulated genes in the mouse genome. Although these genes are scattered around the genome, several regions in chromosomes 7, 17 and 19 show especially high density of diurnally regulated genes.
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Figure 1: A karyotype map showing the chromosome positions and frequencies of diurnally regulated genes in the mouse genome. Although these genes are scattered around the genome, several regions in chromosomes 7, 17 and 19 show especially high density of diurnally regulated genes.

Mentions: C57BL/6J mice were entrained to a 12 hour light and 12 hour dark cycle (LD 12:12) for two weeks. We collected tissue samples at four time points, 3 and 9 hours after lights on (ZT3 and ZT9) and 3 and 9 hours after lights off (ZT15 and ZT21), to gain higher resolution temporal patterns of expression and to capture genes whose expression phases would result in similar levels at two time points. To identify genes with diurnally regulated expression levels, RNA samples from the prefrontal cortex of three mice at each ZT point were used for the preparation of cDNA for microarray expression profiling. We expected that examination of gene expression at four time points during the 24 hour light:dark cycle would permit identification of genes regulated by the circadian clock, those controlled by the sleep:wake states, and those induced or suppressed by a wide range of metabolic and environmental conditions. By probing the Affymetrix high-density chip (the Mouse430_v2 array) with approximately 45,000 probe sets, we identified 3,890 probe sets representing 2,927 unique Ensembl genes with diurnally regulated expression levels in the prefrontal cortex at a false discovery rate (FDR) threshold of 20%. We used a relatively liberal FDR threshold because we aimed at identifying a highly comprehensive list of diurnal genes at the cost of decreased specificity. These genes are distributed throughout the mouse genome (Figure 1), and several regions in chromosomes 7, 17 and 19 are especially enriched with diurnally regulated genes.


Genome-wide expression profiling and bioinformatics analysis of diurnally regulated genes in the mouse prefrontal cortex.

Yang S, Wang K, Valladares O, Hannenhalli S, Bucan M - Genome Biol. (2007)

A karyotype map showing the chromosome positions and frequencies of diurnally regulated genes in the mouse genome. Although these genes are scattered around the genome, several regions in chromosomes 7, 17 and 19 show especially high density of diurnally regulated genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2258187&req=5

Figure 1: A karyotype map showing the chromosome positions and frequencies of diurnally regulated genes in the mouse genome. Although these genes are scattered around the genome, several regions in chromosomes 7, 17 and 19 show especially high density of diurnally regulated genes.
Mentions: C57BL/6J mice were entrained to a 12 hour light and 12 hour dark cycle (LD 12:12) for two weeks. We collected tissue samples at four time points, 3 and 9 hours after lights on (ZT3 and ZT9) and 3 and 9 hours after lights off (ZT15 and ZT21), to gain higher resolution temporal patterns of expression and to capture genes whose expression phases would result in similar levels at two time points. To identify genes with diurnally regulated expression levels, RNA samples from the prefrontal cortex of three mice at each ZT point were used for the preparation of cDNA for microarray expression profiling. We expected that examination of gene expression at four time points during the 24 hour light:dark cycle would permit identification of genes regulated by the circadian clock, those controlled by the sleep:wake states, and those induced or suppressed by a wide range of metabolic and environmental conditions. By probing the Affymetrix high-density chip (the Mouse430_v2 array) with approximately 45,000 probe sets, we identified 3,890 probe sets representing 2,927 unique Ensembl genes with diurnally regulated expression levels in the prefrontal cortex at a false discovery rate (FDR) threshold of 20%. We used a relatively liberal FDR threshold because we aimed at identifying a highly comprehensive list of diurnal genes at the cost of decreased specificity. These genes are distributed throughout the mouse genome (Figure 1), and several regions in chromosomes 7, 17 and 19 are especially enriched with diurnally regulated genes.

Bottom Line: The prefrontal cortex is important in regulating sleep and mood.The diurnal expression patterns were confirmed for 16 out of 18 genes in an independent set of RNA samples.The diurnal genes fall into eight temporal categories with distinct functional attributes, as assessed by Gene Ontology classification and analysis of enriched transcription factor binding sites.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics and Penn Center for Bioinformatics, University of Pennsylvania, Philadelphia, PA 19104, USA. shuzhang@mail.med.upenn.edu

ABSTRACT

Background: The prefrontal cortex is important in regulating sleep and mood. Diurnally regulated genes in the prefrontal cortex may be controlled by the circadian system, by sleep:wake states, or by cellular metabolism or environmental responses. Bioinformatics analysis of these genes will provide insights into a wide-range of pathways that are involved in the pathophysiology of sleep disorders and psychiatric disorders with sleep disturbances.

Results: We examined gene expression in the mouse prefrontal cortex at four time points during a 24 hour (12 hour light:12 hour dark) cycle using microarrays, and identified 3,890 transcripts corresponding to 2,927 genes with diurnally regulated expression patterns. We show that 16% of the genes identified in our study are orthologs of identified clock, clock controlled or sleep/wakefulness induced genes in the mouse liver and suprachiasmatic nucleus, rat cortex and cerebellum, or Drosophila head. The diurnal expression patterns were confirmed for 16 out of 18 genes in an independent set of RNA samples. The diurnal genes fall into eight temporal categories with distinct functional attributes, as assessed by Gene Ontology classification and analysis of enriched transcription factor binding sites.

Conclusion: Our analysis demonstrates that approximately 10% of transcripts have diurnally regulated expression patterns in the mouse prefrontal cortex. Functional annotation of these genes will be important for the selection of candidate genes for behavioral mutants in the mouse and for genetic studies of disorders associated with anomalies in the sleep:wake cycle and circadian rhythm.

Show MeSH
Related in: MedlinePlus