Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of wild type mouse lung after treatement with Bleomycin hydrogen chloride to examine disease progression in pulmonary fibrosis

ABSTRACT: Pulmonary fibrosis was induced by a single tail vein injection of Bleomycin hydrogen chloride (100 mg/kg body weight; 1/3 LD50; Nippon Kayaku Co. Ltd., Tokyo) to 6- to 8-wk-old mice. Mice (3-5/endpoint) were sacrificed 7, 15 and 23 days post Bleomycin administration and RNA samples were extracted from sagittal sections of the left lung lobes. Pooled RNA samples, after reverse transcription and labeling, were hybridized to cDNA microarrays, manufactured by RIKEN, containing 21168 gene probes.

ORGANISM(S): Mus musculus

SUBMITTER: Vaggelis Harokopos

PROVIDER: E-MUGN-1 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Comparative expression profiling in pulmonary fibrosis suggests a role of hypoxia-inducible factor-1alpha in disease pathogenesis.

Tzouvelekis Argyris A Harokopos Vaggelis V Paparountas Triantafillos T Oikonomou Nikos N Chatziioannou Aristotelis A Vilaras George G Tsiambas Evangelos E Karameris Andreas A Bouros Demosthenes D Aidinis Vassilis V

American journal of respiratory and critical care medicine 20070829 11

<h4>Rationale</h4>Despite intense research efforts, the etiology and pathogenesis of idiopathic pulmonary fibrosis remain poorly understood.<h4>Objectives</h4>To discover novel genes and/or cellular pathways involved in the pathogenesis of the disease.<h4>Methods</h4>We performed expression profiling of disease progression in a well-characterized animal model of the disease. Differentially expressed genes that were identified were compared with all publicly available expression profiles both fro ...[more]

PMID: 17761615

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Project description:Transcript elongation by RNA polymerase II (RNAPII) is accompanied by conserved patterns of histone modification within transcribed regions, but it remains uncertain how these modifications influence, or are influenced by, properties of the elongation complex. Here we establish an intimate link between Cdk9, the kinase component of positive transcription elongation factor b (P-TEFb), and mono-ubiquitylation of histone H2B (H2Bub1), in the fission yeast Schizosaccharomyces pombe. Mutations that impair Cdk9 function reduce H2Bub1 levels in vivo. Conversely, mutations that prevent H2Bub1 decrease phosphorylation of elongation factor subunit Spt5, a sensitive and specific indicator of Cdk9 activity. Chromatin immunoprecipitation (ChIP) analysis suggests this is due to impaired Cdk9 recruitment to H2Bub1-deficient chromatin. P-TEFb and H2Bub1 pathways also interact genetically: mutation of the histone H2B ubiquitin-acceptor residue decreases the requirement for Cdk9 activity in vivo, and multiple cdk9 mutations suppress morphological defects of H2Bub1-deficient strains. Moreover, H2Bub1 loss causes redistribution of transcribing RNAPII on chromatin that is corrected by a hypomorphic cdk9 mutation. Therefore, whereas mutual dependence of Spt5 phosphorylation and H2Bub1 suggests positive feedback between P-TEFb and the ubiquitylation machinery, mutual suppression by cdk9 and H2Bub1-pathway mutations indicates an antagonistic relationship, whereby the activities must be balanced to properly regulate elongation. In order to study the genome-wide localization of H2Bub1 in Schizosaccharomyces pombe, H2Bub1, H2B-Flag as well as RNAPII (along with associated DNA sequences) were immunoprecipitated using repectively anti-H2Bub1, anti-Flag and anti-8WG16 antibodies. The ChIPs were performed in duplicate from WT cells as well as in the H2B-K119R mutant. The extracted DNA was hybridized to a DNA microarray containing an average of 4 probes per kilobase across the whole yeast genome. The combined datasets are available in the supplemental files of the related publication.

Dataset Information

Transcription profiling of wild type mouse lung after treatement with Bleomycin hydrogen chloride to examine disease progression in pulmonary fibrosis

Publications

Comparative expression profiling in pulmonary fibrosis suggests a role of hypoxia-inducible factor-1alpha in disease pathogenesis.

Similar Datasets

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