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Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation and is guided by the microbiome

Overview of attention for article published in Genome Biology, September 2015
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (96th percentile)
  • High Attention Score compared to outputs of the same age and source (80th percentile)

Mentioned by

news
5 news outlets
twitter
38 X users
facebook
2 Facebook pages
googleplus
1 Google+ user

Citations

dimensions_citation
113 Dimensions

Readers on

mendeley
184 Mendeley
citeulike
2 CiteULike
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Title
Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation and is guided by the microbiome
Published in
Genome Biology, September 2015
DOI 10.1186/s13059-015-0763-5
Pubmed ID
Authors

Da-Hai Yu, Manasi Gadkari, Quan Zhou, Shiyan Yu, Nan Gao, Yongtao Guan, Deborah Schady, Tony N. Roshan, Miao-Hsueh Chen, Eleonora Laritsky, Zhongqi Ge, Hui Wang, Rui Chen, Caroline Westwater, Lynn Bry, Robert A. Waterland, Chelsea Moriarty, Cindy Hwang, Alton G. Swennes, Sean R. Moore, Lanlan Shen

Abstract

DNA methylation is an epigenetic mechanism central to development and maintenance of complex mammalian tissues, but our understanding of its role in intestinal development is limited. We use whole genome bisulfite sequencing, and find that differentiation of mouse colonic intestinal stem cells to intestinal epithelium is not associated with major changes in DNA methylation. However, we detect extensive dynamic epigenetic changes in intestinal stem cells and their progeny during the suckling period, suggesting postnatal epigenetic development in this stem cell population. We find that postnatal DNA methylation increases at 3' CpG islands (CGIs) correlate with transcriptional activation of glycosylation genes responsible for intestinal maturation. To directly test whether 3' CGI methylation regulates transcription, we conditionally disrupted two major DNA methyltransferases, Dnmt1 or Dnmt3a, in fetal and adult intestine. Deficiency of Dnmt1 causes severe intestinal abnormalities in neonates and disrupts crypt homeostasis in adults, whereas Dnmt3a loss was compatible with intestinal development. These studies reveal that 3' CGI methylation is functionally involved in the regulation of transcriptional activation in vivo, and that Dnmt1 is a critical regulator of postnatal epigenetic changes in intestinal stem cells. Finally, we show that postnatal 3' CGI methylation and associated gene activation in intestinal epithelial cells are significantly altered by germ-free conditions. Our results demonstrate that the suckling period is critical for epigenetic development of intestinal stem cells, with potential important implications for lifelong gut health, and that the gut microbiome guides and/or facilitates these postnatal epigenetic processes.

X Demographics

X Demographics

The data shown below were collected from the profiles of 38 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 184 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 <1%
France 1 <1%
Ireland 1 <1%
Unknown 181 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 37 20%
Researcher 34 18%
Student > Bachelor 22 12%
Student > Master 16 9%
Other 13 7%
Other 27 15%
Unknown 35 19%
Readers by discipline Count As %
Agricultural and Biological Sciences 53 29%
Biochemistry, Genetics and Molecular Biology 37 20%
Medicine and Dentistry 16 9%
Immunology and Microbiology 12 7%
Chemistry 4 2%
Other 20 11%
Unknown 42 23%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 57. 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 07 July 2016.
All research outputs
#757,387
of 25,654,806 outputs
Outputs from Genome Biology
#495
of 4,498 outputs
Outputs of similar age
#10,803
of 286,971 outputs
Outputs of similar age from Genome Biology
#16
of 84 outputs
Altmetric has tracked 25,654,806 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,498 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 27.5. This one has done well, scoring higher than 88% 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 286,971 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 96% of its contemporaries.
We're also able to compare this research output to 84 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.