Dataset Information

DAC for Cardiac Translatomes of 80 Human Samples (65 DCM cases 15 controls)

ABSTRACT: Data Access Committee EGAC00001001040

OTHER RELATED OMICS DATASETS IN: PXD012593

PROVIDER: EGAC00001001040 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Publications

The Translational Landscape of the Human Heart.

van Heesch Sebastiaan S Witte Franziska F Schneider-Lunitz Valentin V Schulz Jana F JF Adami Eleonora E Faber Allison B AB Kirchner Marieluise M Maatz Henrike H Blachut Susanne S Sandmann Clara-Louisa CL Kanda Masatoshi M Worth Catherine L CL Schafer Sebastian S Calviello Lorenzo L Merriott Rhys R Patone Giannino G Hummel Oliver O Wyler Emanuel E Obermayer Benedikt B Mücke Michael B MB Lindberg Eric L EL Trnka Franziska F Memczak Sebastian S Schilling Marcel M Felkin Leanne E LE Barton Paul J R PJR Quaife Nicholas M NM Vanezis Konstantinos K Diecke Sebastian S Mukai Masaya M Mah Nancy N Oh Su-Jun SJ Kurtz Andreas A Schramm Christoph C Schwinge Dorothee D Sebode Marcial M Harakalova Magdalena M Asselbergs Folkert W FW Vink Aryan A de Weger Roel A RA Viswanathan Sivakumar S Widjaja Anissa A AA Gärtner-Rommel Anna A Milting Hendrik H Dos Remedios Cris C Knosalla Christoph C Mertins Philipp P Landthaler Markus M Vingron Martin M Linke Wolfgang A WA Seidman Jonathan G JG Seidman Christine E CE Rajewsky Nikolaus N Ohler Uwe U Cook Stuart A SA Hubner Norbert N

Cell 20190530 1

Gene expression in human tissue has primarily been studied on the transcriptional level, largely neglecting translational regulation. Here, we analyze the translatomes of 80 human hearts to identify new translation events and quantify the effect of translational regulation. We show extensive translational control of cardiac gene expression, which is orchestrated in a process-specific manner. Translation downstream of predicted disease-causing protein-truncating variants appears to be frequent, s ...[more]

PMID: 31155234

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Project description:Reversal of gene promoter DNA hypermethylation and associated abnormal gene silencing is an attractive approach to cancer therapy. The DNA methylation inhibitor, decitabine (5-aza-2'-deoxycitidine), is proving efficacious for hematological neoplasms especially at lower, less toxic, doses. Experimentally, high doses induce rapid DNA damage and cytotoxicity, but these may not explain the prolonged time to response seen in patients. Transient exposure of leukemic and solid tumor cells to clinically-relevant nanomolar doses, without causing immediate cytotoxicity or apoptosis, produces sustained reduced tumorigenicity, and for leukemia cells, diminished long-term self-renewal. These effects appear triggered by cellular reprogramming and include sustained decreases in promoter DNA methylation with associated gene re-expression, and anti-tumor changes in multiple key cellular regulatory pathways, most of which are high priority targets for pharmacologic anti-cancer strategies. Thus, low dose decitabine regimens appear to have broad applicability for cancer management. [Gene expression profiling] Leukemia cell lines Kasumi-1 and KG1A are treated with 10nM DAC during 72 hours and gene expression was assayed at day 3, 7 and 14 after the start of the treatment. Appropriate mock treated samples were used as control in each case. In addition, Kasumi-1 cells were also treated with a higher dose of DAC (500nM), 100nM ARA-C and 300 nM TSA, again controlled against mock treated Kasumi-1 cells, to separate dose and agent dependent effects. MCF7 was studied as an example of a solid tumor cell line. Therefore MCF7 cells were treated with 100nM DAC and results were assayed at day 1, day 3 and day 10. [Methylation profiling] The effects of the demethylating agent DAC were studied in the leukemia cell line Kasumi-1 over a 28 day time course. Intermediate time points were studied at days 3, 7, 14 and 21. These results were verfied in KG1A and KG1 leukemia cell lines, at one selected time point. The effects on one primary sample were also studied. Four normal leukemia samples (PL1, 2, 4 and 5) were used as general controls. The effect of DAC was compared to ARA-C, TSA. Both mock treated and day 3 DAC treated Kasumi-1 cells were repeated. These results were verified at one selected time point for the DAC treated MCF7 breast cancer cell line.

Dataset Information

DAC for Cardiac Translatomes of 80 Human Samples (65 DCM cases 15 controls)

Publications

The Translational Landscape of the Human Heart.

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