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Dynamic resolution of functionally related gene sets in response to acute heat stress.

Szustakowski JD, Kosinski PA, Marrese CA, Lee JH, Elliman SJ, Nirmala N, Kemp DM - BMC Mol. Biol. (2007)

Bottom Line: Protein turnover-related pathways were significantly affected including protein folding, pre-mRNA processing, mRNA splicing, proteolysis and proteasome-related pathways.Many responses were transient, tending to normalize within 24 hours.In summary, we show that the transcriptional response to acute cell stress is largely transient and proteosome-centric.

View Article: PubMed Central - HTML - PubMed

Affiliation: Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA. joseph.szustakowski@novartis.com <joseph.szustakowski@novartis.com>

ABSTRACT

Background: Using a gene clustering strategy we determined intracellular pathway relationships within skeletal myotubes in response to an acute heat stress stimuli. Following heat shock, the transcriptome was analyzed by microarray in a temporal fashion to characterize the dynamic relationship of signaling pathways.

Results: Bioinformatics analyses exposed coordination of functionally-related gene sets, depicting mechanism-based responses to heat shock. Protein turnover-related pathways were significantly affected including protein folding, pre-mRNA processing, mRNA splicing, proteolysis and proteasome-related pathways. Many responses were transient, tending to normalize within 24 hours.

Conclusion: In summary, we show that the transcriptional response to acute cell stress is largely transient and proteosome-centric.

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Related in: MedlinePlus

Temporal gene clusters during response to heat shock of C2C12 myotubes. Temporally upregulated genes were clustered by selection of probes that coregulated with a specific peak time between 1 and 24 hours post-heat shock, as determined from the normalized expression profile data. Expression profiles of each gene within clusters are represented for the entire 24 hour timecourse to reflect the transient nature of expression.
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Figure 2: Temporal gene clusters during response to heat shock of C2C12 myotubes. Temporally upregulated genes were clustered by selection of probes that coregulated with a specific peak time between 1 and 24 hours post-heat shock, as determined from the normalized expression profile data. Expression profiles of each gene within clusters are represented for the entire 24 hour timecourse to reflect the transient nature of expression.

Mentions: Of the approximately 46,000 probes arrayed on the gene chips, the most variable and dynamically regulated were characterized by basic clustering methodology (Figure 2). The most actively regulated group of genes immediately following treatment (ie. 1 hour post heat shock) unsurprisingly comprised a number of heat-shock proteins. hsp1a, hsp1b and hsp8 were among the most significantly upregulated transcripts at this time point (Figure 2A). Gene sets that clustered at 2, 4, 8 and 24 hours following heat shock are displayed in Figure 2 and are partially represented in Table 1. The 8 hour gene set was the largest group that displayed a significant upregulation, and is likely comprised of genes that were regulated downstream of immediate early genes. Therefore, this cluster may represent an important set of genes that functionally dictate the coordinated response of myogenic cells to stress or injury.


Dynamic resolution of functionally related gene sets in response to acute heat stress.

Szustakowski JD, Kosinski PA, Marrese CA, Lee JH, Elliman SJ, Nirmala N, Kemp DM - BMC Mol. Biol. (2007)

Temporal gene clusters during response to heat shock of C2C12 myotubes. Temporally upregulated genes were clustered by selection of probes that coregulated with a specific peak time between 1 and 24 hours post-heat shock, as determined from the normalized expression profile data. Expression profiles of each gene within clusters are represented for the entire 24 hour timecourse to reflect the transient nature of expression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1904231&req=5

Figure 2: Temporal gene clusters during response to heat shock of C2C12 myotubes. Temporally upregulated genes were clustered by selection of probes that coregulated with a specific peak time between 1 and 24 hours post-heat shock, as determined from the normalized expression profile data. Expression profiles of each gene within clusters are represented for the entire 24 hour timecourse to reflect the transient nature of expression.
Mentions: Of the approximately 46,000 probes arrayed on the gene chips, the most variable and dynamically regulated were characterized by basic clustering methodology (Figure 2). The most actively regulated group of genes immediately following treatment (ie. 1 hour post heat shock) unsurprisingly comprised a number of heat-shock proteins. hsp1a, hsp1b and hsp8 were among the most significantly upregulated transcripts at this time point (Figure 2A). Gene sets that clustered at 2, 4, 8 and 24 hours following heat shock are displayed in Figure 2 and are partially represented in Table 1. The 8 hour gene set was the largest group that displayed a significant upregulation, and is likely comprised of genes that were regulated downstream of immediate early genes. Therefore, this cluster may represent an important set of genes that functionally dictate the coordinated response of myogenic cells to stress or injury.

Bottom Line: Protein turnover-related pathways were significantly affected including protein folding, pre-mRNA processing, mRNA splicing, proteolysis and proteasome-related pathways.Many responses were transient, tending to normalize within 24 hours.In summary, we show that the transcriptional response to acute cell stress is largely transient and proteosome-centric.

View Article: PubMed Central - HTML - PubMed

Affiliation: Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA. joseph.szustakowski@novartis.com <joseph.szustakowski@novartis.com>

ABSTRACT

Background: Using a gene clustering strategy we determined intracellular pathway relationships within skeletal myotubes in response to an acute heat stress stimuli. Following heat shock, the transcriptome was analyzed by microarray in a temporal fashion to characterize the dynamic relationship of signaling pathways.

Results: Bioinformatics analyses exposed coordination of functionally-related gene sets, depicting mechanism-based responses to heat shock. Protein turnover-related pathways were significantly affected including protein folding, pre-mRNA processing, mRNA splicing, proteolysis and proteasome-related pathways. Many responses were transient, tending to normalize within 24 hours.

Conclusion: In summary, we show that the transcriptional response to acute cell stress is largely transient and proteosome-centric.

Show MeSH
Related in: MedlinePlus