Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse olfactory epithelium frpm Harlequin mutants compared to littermate controls

ABSTRACT: Microarray analysis of gene expression in the olfactory epithelium of Harlequin mouse as a model of oxidative-stress induced neurodegeneration of olfactory sensory neurons Experiment Overall Design: Olfactory epithelium from Harlequin mutant mice and littermate control mice was microdissected for RNA extraction and hybridization on Affymetrix microarrays. We compared levels of gene expression in 6-month old mice to begin to identify mechanisms of oxidative-stress induced neurodegeneration and to correlate the cellular changes that we observed in the olfactory epithelium by using histology and immunohistochemistry with gene expression changes.

ORGANISM(S): Mus musculus

SUBMITTER: Marilyn Getchell

PROVIDER: E-GEOD-6485 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Cellular and molecular characterization of oxidative stress in olfactory epithelium of Harlequin mutant mouse.

Vaishnav Radhika A RA Getchell Marilyn L ML Huang Liping L Hersh Matthew A MA Stromberg Arnold J AJ Getchell Thomas V TV

Journal of neuroscience research 20080101 1

Oxidative stress in the olfactory system is a major factor associated with age-related olfactory impairment, although the mechanisms by which this occurs are not completely understood. The Harlequin mutant mouse (Hq/Y), which carries an X-linked recessive mutation in the Aifm1 gene, is a model of progressive oxidative stress-induced neurodegeneration in the cerebellum and retina. To determine whether the Hq/Y mutant mouse is a suitable model of oxidative stress-associated olfactory aging, we inv ...[more]

PMID: 17868149

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Project description:Distant enhancer elements are a major source of specificity in mammalian gene expression. Although enhancers that regulate broad developmental decisions and inducible gene expression have been studied extensively, little is known about regulatory elements that govern monogenic and monoallelic expression. Here, using high throughput epigenetic and genetic techniques we identified a plethora of distant enhancers that regulate monoallelic olfactory receptor (OR) gene expression. Potential OR enhancers have unique, cell type specific epigenetic marks that distinguish them from other neuronal enhancers and correlate with enhancer activity in vivo. Using sequence capture to enrich for these sequences we identified Dnase-protected footprints that reveal novel regulatory sequences and transcription factors required for OR gene activation. Our experiments provide insight to the regulation of OR expression, and describe novel principles and methodologies towards the understanding of transcriptional mechanisms that generate cellular diversity. In vivo examination of H3K79me3 enrichment and DNAse protected footprints on olfactory receptor enhancer sequences. We performed ChIP-seq on native chromatin isolated from the mouse olfactory epithelium using antibodies against H3K79me3. To sequence accessible regions of the genome we treated nuclei with limiting amounts of DNAse I to digest accessible chromatin and perform Dnase Hypersensitivity (DHS)-seq. In the olfactory epithelium, the H enhancer – the first described enhancer for olfactory receptors has a well-defined DNAse I hypersensitivity peak and is flanked by high levels of H3K79me3. We find other intergenic sequences nearby olfactory receptor genes that share the same chromatin signature, and test their function in vivo. TO uncover transcription factor footprints on olfactory receptor enhancers we performed sequence capture of the DHS-seq library to enrich for these sequences. We find multiple DNAse-protected sequences and perform motif analysis on transcription factor footprints to reveal factors involved in olfactory receptor gene regulation.

Dataset Information

Transcription profiling of mouse olfactory epithelium frpm Harlequin mutants compared to littermate controls

Publications

Cellular and molecular characterization of oxidative stress in olfactory epithelium of Harlequin mutant mouse.

Similar Datasets

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