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Widespread recovery of methylation at gametic imprints in hypomethylated mouse stem cells following rescue with DNMT3A2

Overview of attention for article published in Epigenetics & Chromatin, November 2016
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Title
Widespread recovery of methylation at gametic imprints in hypomethylated mouse stem cells following rescue with DNMT3A2
Published in
Epigenetics & Chromatin, November 2016
DOI 10.1186/s13072-016-0104-2
Pubmed ID
Authors

Avinash Thakur, Sarah-Jayne Mackin, Rachelle E. Irwin, Karla M. O’Neill, Gareth Pollin, Colum Walsh

Abstract

Imprinted loci are paradigms of epigenetic regulation and are associated with a number of genetic disorders in human. A key characteristic of imprints is the presence of a gametic differentially methylated region (gDMR). Previous studies have indicated that DNA methylation lost from gDMRs could not be restored by DNMT1, or the de novo enzymes DNMT3A or 3B in stem cells, indicating that imprinted regions must instead undergo passage through the germline for reprogramming. However, previous studies were non-quantitative, were unclear on the requirement for DNMT3A/B and showed some inconsistencies. In addition, new putative gDMR has recently been described, along with an improved delineation of the existing gDMR locations. We therefore aimed to re-examine the dependence of methylation at gDMRs on the activities of the methyltransferases in mouse embryonic stem cells (ESCs). We examined the most complete current set of imprinted gDMRs that could be assessed using quantitative pyrosequencing assays in two types of ESCs: those lacking DNMT1 (1KO) and cells lacking a combination of DNMT3A and DNMT3B (3abKO). We further verified results using clonal analysis and combined bisulfite and restriction analysis. Our results showed that loss of methylation was approximately equivalent in both cell types. 1KO cells rescued with a cDNA-expressing DNMT1 could not restore methylation at the imprinted gDMRs, confirming some previous observations. However, nearly all gDMRs were remethylated in 3abKO cells rescued with a DNMT3A2 expression construct (3abKO + 3a2). Transcriptional activity at the H19/Igf2 locus also tracked with the methylation pattern, confirming functional reprogramming in the latter. These results suggested (1) a vital role for DNMT3A/B in methylation maintenance at imprints, (2) that loss of DNMT1 and DNMT3A/B had equivalent effects, (3) that rescue with DNMT3A2 can restore imprints in these cells. This may provide a useful system in which to explore factors influencing imprint reprogramming.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 23 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 26%
Researcher 6 26%
Student > Bachelor 4 17%
Student > Doctoral Student 2 9%
Student > Master 1 4%
Other 1 4%
Unknown 3 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 48%
Agricultural and Biological Sciences 4 17%
Arts and Humanities 1 4%
Pharmacology, Toxicology and Pharmaceutical Science 1 4%
Chemical Engineering 1 4%
Other 2 9%
Unknown 3 13%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 21 January 2018.
All research outputs
#17,870,599
of 22,947,506 outputs
Outputs from Epigenetics & Chromatin
#479
of 568 outputs
Outputs of similar age
#286,891
of 415,683 outputs
Outputs of similar age from Epigenetics & Chromatin
#17
of 17 outputs
Altmetric has tracked 22,947,506 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 568 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one is in the 13th percentile – i.e., 13% 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 415,683 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 17 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.