| 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. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Italy | 1 | 4% |
| Unknown | 26 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 7 | 26% |
| Researcher | 6 | 22% |
| Student > Ph. D. Student | 6 | 22% |
| Student > Postgraduate | 2 | 7% |
| Professor | 1 | 4% |
| Other | 3 | 11% |
| Unknown | 2 | 7% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 8 | 30% |
| Medicine and Dentistry | 6 | 22% |
| Biochemistry, Genetics and Molecular Biology | 5 | 19% |
| Nursing and Health Professions | 2 | 7% |
| Sports and Recreations | 1 | 4% |
| Other | 3 | 11% |
| Unknown | 2 | 7% |
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
#17,736,409
of 22,776,824 outputs
Outputs from Genes & Nutrition
#282
of 388 outputs
Outputs of similar age
#242,996
of 354,743 outputs
Outputs of similar age from Genes & Nutrition
#12
of 15 outputs
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