Identification of coexpressed gene clusters in a comparative analysis of transcriptome and proteome in mouse tissues

Mijalski, T.; Harder, Alois; Halder, Tripti; Kersten, Michael; Horsch, Marion; Strom, Tim M.; Liebscher, Volkmar; Lottspeich, F.; Angelis, Martin Hrabé de; Beckers, Johannes

doi:10.1073/pnas.0407672102

Cited by 77 publications

(61 citation statements)

References 62 publications

(59 reference statements)

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“…Our results help establish consensus and strain-specific patterns of gene expression associated with NAFLD, obesity and diabetes, and identify gene targets for validation studies at the proteome level [37]. With the emergence of transcriptomic data sets derived from NAFLD-susceptible strains [10,13,23], our results contribute to enrichment of the model proposed for disease pathogenesis [5] with novel insights into mechanisms regulating gene expression and novel diet-reactive molecular components, including predicted or poorly annotated genes.…”

Section: Discussionmentioning

confidence: 79%

Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice

et al. 2007

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Aims/hypothesis Complex changes in gene expression are associated with insulin resistance and non-alcoholic fatty liver disease (NAFLD) promoted by feeding a high-fat diet (HFD). We used functional genomic technologies to document molecular mechanisms associated with dietinduced NAFLD. Materials and Methods Male 129S6 mice were fed a diet containing 40% fat (high-fat diet, HFD) for 15 weeks. Glucose tolerance, in vivo insulin secretion, plasma lipid profile and adiposity were determined. Plasma metabonomics and liver transcriptomics were used to identify changes in gene expression associated with HFD-induced NAFLD.Results In HFD-fed mice, NAFLD and impaired glucose and lipid homeostasis were associated with increased hepatic transcription of genes involved in fatty acid uptake, intracellular transport, modification and elongation, whilst genes involved in beta-oxidation and lipoprotein secretion were, paradoxically, also upregulated. NAFLD developed despite strong and sustained downregulation of transcription of the gene encoding stearoyl-coenzyme A desaturase 1 (Scd1) and uncoordinated regulation of transcription of Scd1 and the gene encoding sterol regulatory element binding factor 1c (Srebf1c) transcription. Inflammatory mechanisms appeared to be stimulated by HFD. Conclusions/interpretation Our results provide an accurate representation of subtle changes in metabolic and gene expression regulation underlying disease-promoting and compensatory mechanisms, collectively contributing to dietinduced insulin resistance and NAFLD. They suggest that proposed models of NAFLD pathogenesis can be enriched with novel diet-reactive genes and disease mechanisms.

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Section: Discussionmentioning

confidence: 79%

Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice

et al. 2007

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“…The highly expressed domains (called ridges) are gene dense, GC rich, and SINE repeat rich, and the genes have short introns, whereas the weakly expressed domains (called anti-ridges) show the opposite characteristics (Lercher et al 2003;Versteeg et al 2003). Ridges were also described in the mouse genome (Mijalski et al 2005) and were found to be relatively conserved compared to the human genome .…”

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confidence: 99%

Domain-wide regulation of gene expression in the human genome

Gierman¹,

Indemans²,

Koster³

et al. 2007

Genome Res.

131

125

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Transcription factor complexes bind to regulatory sequences of genes, providing a system of individual expression regulation. Targets of distinct transcription factors usually map throughout the genome, without clustering. Nevertheless, highly and weakly expressed genes do cluster in separate chromosomal domains with an average size of 80-90 genes. We therefore asked whether, besides transcription factors, an additional level of gene expression regulation exists that acts on chromosomal domains. Here we show that identical green fluorescent protein (GFP) reporter constructs integrated at 90 different chromosomal positions obtain expression levels that correspond to the activity of the domains of integration. These domains are up to 80 genes long and can exert an eightfold effect on the expression levels of integrated genes. 3D-FISH shows that active domains of integration have a more open chromatin structure than integration domains with weak activity. These results reveal a novel domain-wide regulatory mechanism that, together with transcription factors, exerts a dual control over gene transcription.

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“…Gene expression arrays can determine the simultaneous profiling of thousands of transcripts. Because transcript expression correlates with protein expression in murine tissues (25)(26)(27), the transcriptome results may be used as a general indicator of protein levels. Using these approaches, we describe the relationship between network neural activity and genome-wide expression profile, and hence the temporal sequence of events that underlie synaptogenesis.…”

mentioning

confidence: 99%

Network activity-independent coordinated gene expression program for synapse assembly

Valor

Charlesworth²,

Humphreys³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Global biological datasets generated by genomics, transcriptomics, and proteomics provide new approaches to understanding the relationship between the genome and the synapse. Combined transcriptome analysis and multielectrode recordings of neuronal network activity were used in mouse embryonic primary neuronal cultures to examine synapse formation and activity-dependent gene regulation. Evidence for a coordinated gene expression program for assembly of synapses was observed in the expression of 642 genes encoding postsynaptic and plasticity proteins. This synaptogenesis gene expression program preceded protein expression of synapse markers and onset of spiking activity. Continued expression was followed by maturation of morphology and electrical neuronal networks, which was then followed by the expression of activity-dependent genes. Thus, two distinct sequentially active gene expression programs underlie the genomic programs of synapse function.synaptogenesis ͉ transcriptome ͉ microarray ͉ multielectrode array

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Identification of coexpressed gene clusters in a comparative analysis of transcriptome and proteome in mouse tissues

Cited by 77 publications

References 62 publications

Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice

Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice

Domain-wide regulation of gene expression in the human genome

Network activity-independent coordinated gene expression program for synapse assembly

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