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γ-Glutamyl hydrolase modulation significantly influences global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells

Overview of attention for article published in Genes & Nutrition, December 2014
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20 Mendeley
Title
γ-Glutamyl hydrolase modulation significantly influences global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells
Published in
Genes & Nutrition, December 2014
DOI 10.1007/s12263-014-0444-0
Pubmed ID
Authors

Sung-Eun Kim, Toshinori Hinoue, Michael S. Kim, Kyoung-Jin Sohn, Robert C. Cho, Peter D. Cole, Daniel J. Weisenberger, Peter W. Laird, Young-In Kim

Abstract

γ-Glutamyl hydrolase (GGH) plays an important role in folate homeostasis by catalyzing hydrolysis of polyglutamylated folate into monoglutamates. Polyglutamylated folates are better substrates for several enzymes involved in the generation of S-adenosylmethionine, the primary methyl group donor, and hence, GGH modulation may affect DNA methylation. DNA methylation is an important epigenetic determinant in gene expression, in the maintenance of DNA integrity and stability, and in chromatin modifications, and aberrant or dysregulation of DNA methylation has been mechanistically linked to the development of human diseases including cancer. Using a recently developed in vitro model of GGH modulation in HCT116 colon and MDA-MB-435 breast cancer cells, we investigated whether GGH modulation would affect global and gene-specific DNA methylation and whether these alterations were associated with significant gene expression changes. In both cell lines, GGH overexpression decreased global DNA methylation and DNA methyltransferase (DNMT) activity, while GGH inhibition increased global DNA methylation and DNMT activity. Epigenomic and gene expression analyses revealed that GGH modulation influenced CpG promoter DNA methylation and gene expression involved in important biological pathways including cell cycle, cellular development, and cellular growth and proliferation. Some of the observed altered gene expression appeared to be regulated by changes in CpG promoter DNA methylation. Our data suggest that the GGH modulation-induced changes in total intracellular folate concentrations and content of long-chain folylpolyglutamates are associated with functionally significant DNA methylation alterations in several important biological pathways.

Twitter Demographics

The data shown below were collected from the profiles of 2 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 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Italy 1 5%
Unknown 19 95%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 25%
Student > Ph. D. Student 3 15%
Student > Master 3 15%
Unspecified 2 10%
Student > Postgraduate 2 10%
Other 5 25%
Readers by discipline Count As %
Agricultural and Biological Sciences 8 40%
Medicine and Dentistry 6 30%
Biochemistry, Genetics and Molecular Biology 3 15%
Unspecified 2 10%
Social Sciences 1 5%
Other 0 0%

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 08 January 2015.
All research outputs
#9,560,610
of 12,445,334 outputs
Outputs from Genes & Nutrition
#225
of 315 outputs
Outputs of similar age
#174,380
of 279,017 outputs
Outputs of similar age from Genes & Nutrition
#9
of 11 outputs
Altmetric has tracked 12,445,334 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 315 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 24th percentile – i.e., 24% 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 279,017 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 11 others from the same source and published within six weeks on either side of this one. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.