Unknown,Transcriptomics,Genomics,Proteomics

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Exploration of the genes affecting the compound acting against emphysema development in a mouse model of elastase-induced emphysema.

ABSTRACT: In a mouse model of elastase-induced emphysema, the effect of tetomilast against the emphysema development observed in C57BL/6J (C57) could be also detected in phosphodiesterase (PDE) 4D(+/+) but not in PDE4B(+/+), PDE4B(-/-), and PDE4D(-/-) mice. Based on this result, we hypothesized that the difference in the efficacy of tetomilast among these strains of mice might result from the differences in the levels of the target molecules of tetomilast other than PDE4 in each mouse strain. To test this hypothesis, we used microarrays to compare the expression levels of genes in the lungs of each mouse strain. The expression profiling by array demonstrated that the levels of cyclin-dependent kinase inhibitor 1 (CDKN1a) in PDE4B(+/+), PDE4B(-/-), and PDE4D(-/-) were higher than those in C57 and PDE4D(+/+). Total RNAs were extracted from the lungs from naÃ¯ve mice in each strain [C57, PDE4B(+/+), PDE4B(-/-), PDE4D(+/+), and PDE4D(-/)], and were used for microarray. In comparison with the expression levels of genes in C57, we retrieved the genes which expressed at the same levels in PDE4D(+/+), and at the different levels in PDE4B(+/+), PDE4B(-/-), and PDE4D(-/-).

ORGANISM(S): Mus musculus

SUBMITTER: Hisashi Nagamoto

PROVIDER: E-GEOD-85962 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The local protein composition of chromatin is important for the regulation of transcription and other functions. By integrative analysis of genome-wide binding maps of 53 broadly selected chromatin components in Drosophila cells, we show that the genome is segmented into five principal chromatin types that are defined by unique, yet overlapping combinations of proteins, and form domains that can extend over >100 kb. We identify a novel repressive chromatin type that covers about half of the genome and lacks classic heterochromatin markers. Furthermore, transcriptionally active euchromatin consists of two distinct types that differ in molecular organization and H3K36 methylation, and regulate distinct classes of genes. Finally, we provide evidence that the different chromatin types act as guides that help to target DNA-binding factors to specific subsets of their recognition motifs. These results uncover basic principles of chromatin organization in a higher eukaryote. For this study, we generated whole-genome DamID binding profiles of 45 chromatin proteins in Drosophila Kc167 cells. Additionally, we perused published binding data of 8 chromatin proteins and generated a binding profile of one exogenous (yeast) DNA binding factor in Kc167 cells. On the same array platform, we obtained ChIP-on-chip profiles of histone H3, H1, H3K9me2, H3K27me3, H3K4me2, and H3K79me3. See supplementary files below. Gene expression was measured by RNA tag profiling. See GeneCounts supplementary file below. [1] RNA tag sequences were optained on an Illumina GAII with the digital gene expression (DGE) module from duplicate RNA samples. [2] All DamID and ChIP experiments were done in Drosophila Kc167 cells in duplicate. Samples were hybridized to 380k NimbleGen arrays with 300 bp probe spacing. Every experiment was done in duplicate in the reverse dye orientation, where Dam-fusion material was hybridized over Dam-only material. For ChIP, immunoprecipitated material was hybridized over ChIP input material. 18 previously-submitted Samples were included in this study. 10 of 18 Samples have been renormalized for the GSE22069 study: GSM509087, GSM509088, GSM509089, GSM509090, GSM509091, GSM509092, GSM509093, GSM509094, GSM509095, GSM509096 New GSM accession numbers have been issued for these 10 samples. 8 of 18 Samples are identical in the original studies and in GSE22069: GSM423290, GSM423291, GSM423298, GSM423299, GSM493592, GSM493593, GSM509085, GSM509086 [3] The genomic locations in files GSE22069_norm_aggregated_discretized_tiling_arrays.txt and GSE22069_norm_aggregated_tiling_arrays.txt are relative to FlyBase release 5 (BDGP R5/dm3).

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Exploration of the genes affecting the compound acting against emphysema development in a mouse model of elastase-induced emphysema.

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