Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Short RNAs profiling and chromatin immunoprecipitation of human CD4+ T-cells to measure histone modifications and RNA pol II at short RNA loci

ABSTRACT: Detection of short RNAs in human CD4+ T-cells and measurements of histone modifications and RNA pol II at short RNA loci

ORGANISM(S): Homo sapiens

SUBMITTER: Richard Jenner

PROVIDER: E-TABM-844 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2.

Kanhere Aditi A Viiri Keijo K Araújo Carla C CC Rasaiyaah Jane J Bouwman Russell D RD Whyte Warren A WA Pereira C Filipe CF Brookes Emily E Walker Kimberly K Bell George W GW Pombo Ana A Fisher Amanda G AG Young Richard A RA Jenner Richard G RG

Molecular cell 20100601 5

Polycomb proteins maintain cell identity by repressing the expression of developmental regulators specific for other cell types. Polycomb repressive complex-2 (PRC2) catalyzes trimethylation of histone H3 lysine-27 (H3K27me3). Although repressed, PRC2 targets are generally associated with the transcriptional initiation marker H3K4me3, but the significance of this remains unclear. Here, we identify a class of short RNAs, approximately 50-200 nucleotides in length, transcribed from the 5' end of p ...[more]

PMID: 20542000

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Project description:Nkx2.1 is a critical regulator of mammalian lung development. It is expressed in epithelial cells at the initiation of lung organogenesis, becoming progressively restricted during development to bronchiolar and alveolar type II epithelial cells. In humans, it is a common marker of carcinomas of lung and thyroid origin and is highly amplified in 10-15% of lung adenocarcinomas. Despite its key role in development and disease only a few genes directly regulated by Nkx2.1 are known. To identify direct Nkx2.1target genes and pathways controlled by this transcription factor in vivo we analyzed, by chromatin immuno-precipitation (chip)-on-chip method, Nkx2.1 binding to DNA cis-elements in developing mouse lung. We analyzed embryonic day E11.5 lungs, when Nkx2.1 expressing cells are undergoing predominantly proliferation, and day E19.5, when Nkx2.1 expressing cells are undergoing predominantly differentiation. Many highly bound targets are known and well described, such as surfactant proteins and secretoglobins. Unique or common target genes involved in a variety of developmental and tumorigenic pathways were identified at each developmental time point. Positive regulation of cell proliferation was the highest overrepresented biological process at E11.5 while ion transport was the highest overrepresented biological process at E19.5. New identified targets include proliferation related genes such as E2F3, Met, Ccnb1, and Ccnb2. Nkx2.1 downregulation in mouse epithelial and human carcinoma cell lines reduced cell proliferation by arresting cells in the G2/M phase. Reduced expression of Nkx2.1 target genes in both cell lines supports a direct role of Nkx2.1 in regulation of cell proliferation genes. The identification of these transcriptional regulatory pathways in vivo aid us to understand Nkx2.1 function in lung development and link it to disease, since many of the identified targets are aberrantly up regulated in cancer cells. Developing mouse lung, 2 developmental time points E11.5 and E19.5, genomic DNA fragments immunoprecipitated with a-Nkx2.1 (07-601, Upstate-Millipore) vs input, E11.5, 2 biological replicates and E19.5, 3 biological replicates

Dataset Information

Short RNAs profiling and chromatin immunoprecipitation of human CD4+ T-cells to measure histone modifications and RNA pol II at short RNA loci

Publications

Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2.

Similar Datasets

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