Dataset Information

Molecular and Population Genetics (MPG) research at ICR DAC agreement

ABSTRACT: Data Access Committee EGAC00001000303

PROVIDER: EGAC00001000303 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Publications

Capture Hi-C identifies the chromatin interactome of colorectal cancer risk loci.

Jäger Roland R Migliorini Gabriele G Henrion Marc M Kandaswamy Radhika R Speedy Helen E HE Heindl Andreas A Whiffin Nicola N Carnicer Maria J MJ Broome Laura L Dryden Nicola N Nagano Takashi T Schoenfelder Stefan S Enge Martin M Yuan Yinyin Y Taipale Jussi J Fraser Peter P Fletcher Olivia O Houlston Richard S RS

Nature communications 20150219

Multiple regulatory elements distant from their targets on the linear genome can influence the expression of a single gene through chromatin looping. Chromosome conformation capture implemented in Hi-C allows for genome-wide agnostic characterization of chromatin contacts. However, detection of functional enhancer-promoter interactions is precluded by its effective resolution that is determined by both restriction fragmentation and sensitivity of the experiment. Here we develop a capture Hi-C (c ...[more]

PMID: 25695508

Similar Datasets

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

Molecular and Population Genetics (MPG) research at ICR DAC agreement

Publications

Capture Hi-C identifies the chromatin interactome of colorectal cancer risk loci.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure