Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profiling of liver from regulatar chow (RC) fed-mice, high fat diet (HFD)-fed mice with vehicle or nobiletin (NOB) treatment

ABSTRACT: Comparison of liver transcriptome between RC-fed mice, HFD-fed mice with vehicle or nobiletin treatment provides the possibility to identify the effects of nobiletin on gene expression altered by HFD relative to RC. We used Illumina microarrays to analyze liver transcriptome of different treatment groups following exposure to RC, HFD.Veh (denoted as the HFD group) and HFD.NOB (denoted as the NOB group). The microarray experiment was performed to investigate effects of HFD and NOB on mouse liver transcriptome. Liver tissues were collected at ZT2 and ZT14 (corresponding to 2 hours after light on and light off, respectively). The pooled RNA samples, 4 mice each group, were used for the microarray.

ORGANISM(S): Mus musculus

SUBMITTER: Zheng Chen

PROVIDER: E-GEOD-78848 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Although majority of the genes linked to pediatric cataract exhibit lens fiber cell-enriched expression, our understanding of gene regulation in these cells is limited to function of just eight transcription factors and largely in the context of crystallins. Here, we identify small Maf transcription factors MafG and MafK as regulators of several non-crystallin human cataract genes in fiber cells and establish their significance to cataract. We applied a bioinformatics tool for cataract gene discovery iSyTE to identify MafG and its co-regulators in the lens, and generated various null-allelic combinations of MafG:MafK mouse mutants for phenotypic and molecular analysis. By age 4-months, MafG-/-:MafK+/- mutants exhibit lens defects that progressively develop into cataract. High-resolution phenotypic characterization of MafG-/-:MafK+/- lens reveals severe defects in fiber cells, while microarrays-based expression profiling identifies 97 differentially regulated genes (DRGs). Integrative analysis of MafG-/-:MafK+/- lens-DRGs with 1) binding-motifs and genomic targets of small Mafs and their regulatory partners, 2) iSyTE lens-expression data, and 3) interactions between DRGs in the String database, unravels a detailed small Maf regulatory network in the lens, several nodes of which are linked to human cataract. This analysis prioritizes 36 highly promising candidates from the original 97 DRGs. Significantly, 8/36 (22%) DRGs are associated with cataracts in human (GSTO1, MGST1, SC4MOL, UCHL1) or mouse (Aldh3a1, Crygf, Hspb1, Pcbd1), suggesting a multifactorial etiology that includes elevation of oxidative stress. These data identify MafG and MafK as new cataract-associated candidates and define their function in regulating largely non-crystallin genes linked to mouse and human cataract. Microarray comparision of lenses from mixed background (129Sv/J, C57BL/6J, and ICR) control (MafG+/-:MafK+/-; no-cataract) and compound (MafG-/-:MafK+/-; cataract) mouse mutants

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Gene expression profiling of liver from regulatar chow (RC) fed-mice, high fat diet (HFD)-fed mice with vehicle or nobiletin (NOB) treatment

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