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Stabilization of Foxp3 expression by CRISPR-dCas9-based epigenome editing in mouse primary T cells

Overview of attention for article published in Epigenetics & Chromatin, May 2017
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (73rd percentile)

Mentioned by

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7 tweeters
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4 patents
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1 Facebook page

Citations

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70 Dimensions

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135 Mendeley
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Title
Stabilization of Foxp3 expression by CRISPR-dCas9-based epigenome editing in mouse primary T cells
Published in
Epigenetics & Chromatin, May 2017
DOI 10.1186/s13072-017-0129-1
Pubmed ID
Authors

Masahiro Okada, Mitsuhiro Kanamori, Kazue Someya, Hiroko Nakatsukasa, Akihiko Yoshimura

Abstract

Epigenome editing is expected to manipulate transcription and cell fates and to elucidate the gene expression mechanisms in various cell types. For functional epigenome editing, assessing the chromatin context-dependent activity of artificial epigenetic modifier is required. In this study, we applied clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-based epigenome editing to mouse primary T cells, focusing on the Forkhead box P3 (Foxp3) gene locus, a master transcription factor of regulatory T cells (Tregs). The Foxp3 gene locus is regulated by combinatorial epigenetic modifications, which determine the Foxp3 expression. Foxp3 expression is unstable in transforming growth factor beta (TGF-β)-induced Tregs (iTregs), while stable in thymus-derived Tregs (tTregs). To stabilize Foxp3 expression in iTregs, we introduced dCas9-TET1CD (dCas9 fused to the catalytic domain (CD) of ten-eleven translocation dioxygenase 1 (TET1), methylcytosine dioxygenase) and dCas9-p300CD (dCas9 fused to the CD of p300, histone acetyltransferase) with guide RNAs (gRNAs) targeted to the Foxp3 gene locus. Although dCas9-TET1CD induced partial demethylation in enhancer region called conserved non-coding DNA sequences 2 (CNS2), robust Foxp3 stabilization was not observed. In contrast, dCas9-p300CD targeted to the promoter locus partly maintained Foxp3 transcription in cultured and primary T cells even under inflammatory conditions in vitro. Furthermore, dCas9-p300CD promoted expression of Treg signature genes and enhanced suppression activity in vitro. Our results showed that artificial epigenome editing modified the epigenetic status and gene expression of the targeted loci, and engineered cellular functions in conjunction with endogenous epigenetic modification, suggesting effective usage of these technologies, which help elucidate the relationship between chromatin states and gene expression.

Twitter Demographics

The data shown below were collected from the profiles of 7 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 135 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Slovenia 1 <1%
Unknown 134 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 30 22%
Researcher 25 19%
Student > Bachelor 18 13%
Student > Master 16 12%
Student > Postgraduate 9 7%
Other 23 17%
Unknown 14 10%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 46 34%
Agricultural and Biological Sciences 34 25%
Immunology and Microbiology 18 13%
Medicine and Dentistry 8 6%
Pharmacology, Toxicology and Pharmaceutical Science 3 2%
Other 7 5%
Unknown 19 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. 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 16 September 2021.
All research outputs
#4,211,317
of 20,993,108 outputs
Outputs from Epigenetics & Chromatin
#179
of 540 outputs
Outputs of similar age
#74,281
of 282,541 outputs
Outputs of similar age from Epigenetics & Chromatin
#1
of 1 outputs
Altmetric has tracked 20,993,108 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 540 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.4. This one has gotten more attention than average, scoring higher than 66% of its peers.
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 282,541 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 73% 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