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A high-throughput screen of inactive X chromosome reactivation identifies the enhancement of DNA demethylation by 5-aza-2′-dC upon inhibition of ribonucleotide reductase

Overview of attention for article published in Epigenetics & Chromatin, October 2015
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (57th percentile)

Mentioned by

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4 tweeters

Citations

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30 Dimensions

Readers on

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61 Mendeley
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1 CiteULike
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Title
A high-throughput screen of inactive X chromosome reactivation identifies the enhancement of DNA demethylation by 5-aza-2′-dC upon inhibition of ribonucleotide reductase
Published in
Epigenetics & Chromatin, October 2015
DOI 10.1186/s13072-015-0034-4
Pubmed ID
Authors

Alissa Minkovsky, Anna Sahakyan, Giancarlo Bonora, Robert Damoiseaux, Elizabeth Dimitrova, Liudmilla Rubbi, Matteo Pellegrini, Caius G. Radu, Kathrin Plath

Abstract

DNA methylation is important for the maintenance of the silent state of genes on the inactive X chromosome (Xi). Here, we screened for siRNAs and chemicals that reactivate an Xi-linked reporter in the presence of 5-aza-2'-deoxycytidine (5-aza-2'-dC), an inhibitor of DNA methyltransferase 1, at a concentration that, on its own, is not sufficient for Xi-reactivation. We found that inhibition of ribonucleotide reductase (RNR) induced expression of the reporter. RNR inhibition potentiated the effect of 5-aza-2'-dC by enhancing its DNA incorporation, thereby decreasing DNA methylation levels genome-wide. Since both 5-aza-2'-dC and RNR-inhibitors are used in the treatment of hematological malignancies, we treated myeloid leukemia cell lines with 5-aza-2'-dC and the RNR-inhibitor hydroxyurea, and observed synergistic inhibition of cell growth and a decrease in genome-wide DNA methylation. Taken together, our study identifies a drug combination that enhances DNA demethylation by altering nucleotide metabolism. This demonstrates that Xi-reactivation assays can be used to optimize the epigenetic activity of drug combinations.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 61 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
Unknown 60 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 15 25%
Researcher 11 18%
Student > Bachelor 9 15%
Student > Master 9 15%
Professor > Associate Professor 4 7%
Other 6 10%
Unknown 7 11%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 23 38%
Agricultural and Biological Sciences 17 28%
Engineering 2 3%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Earth and Planetary Sciences 1 2%
Other 8 13%
Unknown 8 13%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 November 2015.
All research outputs
#9,861,818
of 17,612,488 outputs
Outputs from Epigenetics & Chromatin
#319
of 492 outputs
Outputs of similar age
#110,370
of 260,363 outputs
Outputs of similar age from Epigenetics & Chromatin
#1
of 1 outputs
Altmetric has tracked 17,612,488 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 492 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.4. This one is in the 34th percentile – i.e., 34% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 260,363 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 57% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them