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In vivo genome-wide profiling reveals a tissue-specific role for 5-formylcytosine

Overview of attention for article published in Genome Biology, June 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (90th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (60th percentile)

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Title
In vivo genome-wide profiling reveals a tissue-specific role for 5-formylcytosine
Published in
Genome Biology, June 2016
DOI 10.1186/s13059-016-1001-5
Pubmed ID
Authors

Mario Iurlaro, Gordon R. McInroy, Heather E. Burgess, Wendy Dean, Eun-Ang Raiber, Martin Bachman, Dario Beraldi, Shankar Balasubramanian, Wolf Reik

Abstract

Genome-wide methylation of cytosine can be modulated in the presence of TET and thymine DNA glycosylase (TDG) enzymes. TET is able to oxidise 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). TDG can excise the oxidative products 5fC and 5caC, initiating base excision repair. These modified bases are stable and detectable in the genome, suggesting that they could have epigenetic functions in their own right. However, functional investigation of the genome-wide distribution of 5fC has been restricted to cell culture-based systems, while its in vivo profile remains unknown. Here, we describe the first analysis of the in vivo genome-wide profile of 5fC across a range of tissues from both wild-type and Tdg-deficient E11.5 mouse embryos. Changes in the formylation profile of cytosine upon depletion of TDG suggest TET/TDG-mediated active demethylation occurs preferentially at intron-exon boundaries and reveals a major role for TDG in shaping 5fC distribution at CpG islands. Moreover, we find that active enhancer regions specifically exhibit high levels of 5fC, resulting in characteristic tissue-diagnostic patterns, which suggest a role in embryonic development. The tissue-specific distribution of 5fC can be regulated by the collective contribution of TET-mediated oxidation and excision by TDG. The in vivo profile of 5fC during embryonic development resembles that of embryonic stem cells, sharing key features including enrichment of 5fC in enhancer and intragenic regions. Additionally, by investigating mouse embryo 5fC profiles in a tissue-specific manner, we identify targeted enrichment at active enhancers involved in tissue development.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 126 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 3 2%
Portugal 1 <1%
Belgium 1 <1%
Unknown 121 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 37 29%
Researcher 29 23%
Student > Master 20 16%
Student > Postgraduate 8 6%
Professor 4 3%
Other 16 13%
Unknown 12 10%
Readers by discipline Count As %
Agricultural and Biological Sciences 44 35%
Biochemistry, Genetics and Molecular Biology 33 26%
Chemistry 15 12%
Medicine and Dentistry 5 4%
Unspecified 4 3%
Other 12 10%
Unknown 13 10%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 18. 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 28 October 2017.
All research outputs
#2,020,397
of 25,380,192 outputs
Outputs from Genome Biology
#1,712
of 4,461 outputs
Outputs of similar age
#35,735
of 365,763 outputs
Outputs of similar age from Genome Biology
#26
of 66 outputs
Altmetric has tracked 25,380,192 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,461 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 27.6. This one has gotten more attention than average, scoring higher than 61% 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 365,763 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 90% of its contemporaries.
We're also able to compare this research output to 66 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.