Increased DNA methylation of SLFN12 in CD4+ and CD8+ T cells from multiple sclerosis patients.
DNA methylation is an epigenetic mark that is influenced by environmental factors and is associated with changes to gene expression and phenotypes. It may link environmental exposures to disease etiology or indicate important gene pathways involved in disease pathogenesis. We identified genomic regi...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6209300?pdf=render |
| _version_ | 1818282306556657664 |
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| author | Brooke Rhead Ina S Brorson Tone Berge Cameron Adams Hong Quach Stine Marit Moen Pål Berg-Hansen Elisabeth Gulowsen Celius Dipen P Sangurdekar Paola G Bronson Rodney A Lea Sean Burnard Vicki E Maltby Rodney J Scott Jeannette Lechner-Scott Hanne F Harbo Steffan D Bos Lisa F Barcellos |
| author_facet | Brooke Rhead Ina S Brorson Tone Berge Cameron Adams Hong Quach Stine Marit Moen Pål Berg-Hansen Elisabeth Gulowsen Celius Dipen P Sangurdekar Paola G Bronson Rodney A Lea Sean Burnard Vicki E Maltby Rodney J Scott Jeannette Lechner-Scott Hanne F Harbo Steffan D Bos Lisa F Barcellos |
| author_sort | Brooke Rhead |
| collection | DOAJ |
| description | DNA methylation is an epigenetic mark that is influenced by environmental factors and is associated with changes to gene expression and phenotypes. It may link environmental exposures to disease etiology or indicate important gene pathways involved in disease pathogenesis. We identified genomic regions that are differentially methylated in T cells of patients with relapsing remitting multiple sclerosis (MS) compared to healthy controls. DNA methylation was assessed at 450,000 genomic sites in CD4+ and CD8+ T cells purified from peripheral blood of 94 women with MS and 94 healthy women, and differentially methylated regions were identified using bumphunter. Differential DNA methylation was observed near four loci: MOG/ZFP57, HLA-DRB1, NINJ2/LOC100049716, and SLFN12. Increased methylation of the first exon of the SLFN12 gene was observed in both T cell subtypes and remained present after restricting analyses to samples from patients who had never been on treatment or had been off treatment for more than 2.5 years. Genes near the regions of differential methylation in T cells were assessed for differential expression in whole blood samples from a separate population of 1,329 women with MS and 97 healthy women. Gene expression of HLA-DRB1, NINJ2, and SLFN12 was observed to be decreased in whole blood in MS patients compared to controls. We conclude that T cells from MS patients display regions of differential DNA methylation compared to controls, and corresponding gene expression differences are observed in whole blood. Two of the genes that showed both methylation and expression differences, NINJ2 and SLFN12, have not previously been implicated in MS. SLFN12 is a particularly compelling target of further research, as this gene is known to be down-regulated during T cell activation and up-regulated by type I interferons (IFNs), which are used to treat MS. |
| first_indexed | 2024-12-13T00:18:55Z |
| format | Article |
| id | doaj.art-f7193d155a0b49f58deed8a0dedea550 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T00:18:55Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f7193d155a0b49f58deed8a0dedea5502022-12-22T00:05:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011310e020651110.1371/journal.pone.0206511Increased DNA methylation of SLFN12 in CD4+ and CD8+ T cells from multiple sclerosis patients.Brooke RheadIna S BrorsonTone BergeCameron AdamsHong QuachStine Marit MoenPål Berg-HansenElisabeth Gulowsen CeliusDipen P SangurdekarPaola G BronsonRodney A LeaSean BurnardVicki E MaltbyRodney J ScottJeannette Lechner-ScottHanne F HarboSteffan D BosLisa F BarcellosDNA methylation is an epigenetic mark that is influenced by environmental factors and is associated with changes to gene expression and phenotypes. It may link environmental exposures to disease etiology or indicate important gene pathways involved in disease pathogenesis. We identified genomic regions that are differentially methylated in T cells of patients with relapsing remitting multiple sclerosis (MS) compared to healthy controls. DNA methylation was assessed at 450,000 genomic sites in CD4+ and CD8+ T cells purified from peripheral blood of 94 women with MS and 94 healthy women, and differentially methylated regions were identified using bumphunter. Differential DNA methylation was observed near four loci: MOG/ZFP57, HLA-DRB1, NINJ2/LOC100049716, and SLFN12. Increased methylation of the first exon of the SLFN12 gene was observed in both T cell subtypes and remained present after restricting analyses to samples from patients who had never been on treatment or had been off treatment for more than 2.5 years. Genes near the regions of differential methylation in T cells were assessed for differential expression in whole blood samples from a separate population of 1,329 women with MS and 97 healthy women. Gene expression of HLA-DRB1, NINJ2, and SLFN12 was observed to be decreased in whole blood in MS patients compared to controls. We conclude that T cells from MS patients display regions of differential DNA methylation compared to controls, and corresponding gene expression differences are observed in whole blood. Two of the genes that showed both methylation and expression differences, NINJ2 and SLFN12, have not previously been implicated in MS. SLFN12 is a particularly compelling target of further research, as this gene is known to be down-regulated during T cell activation and up-regulated by type I interferons (IFNs), which are used to treat MS.http://europepmc.org/articles/PMC6209300?pdf=render |
| spellingShingle | Brooke Rhead Ina S Brorson Tone Berge Cameron Adams Hong Quach Stine Marit Moen Pål Berg-Hansen Elisabeth Gulowsen Celius Dipen P Sangurdekar Paola G Bronson Rodney A Lea Sean Burnard Vicki E Maltby Rodney J Scott Jeannette Lechner-Scott Hanne F Harbo Steffan D Bos Lisa F Barcellos Increased DNA methylation of SLFN12 in CD4+ and CD8+ T cells from multiple sclerosis patients. PLoS ONE |
| title | Increased DNA methylation of SLFN12 in CD4+ and CD8+ T cells from multiple sclerosis patients. |
| title_full | Increased DNA methylation of SLFN12 in CD4+ and CD8+ T cells from multiple sclerosis patients. |
| title_fullStr | Increased DNA methylation of SLFN12 in CD4+ and CD8+ T cells from multiple sclerosis patients. |
| title_full_unstemmed | Increased DNA methylation of SLFN12 in CD4+ and CD8+ T cells from multiple sclerosis patients. |
| title_short | Increased DNA methylation of SLFN12 in CD4+ and CD8+ T cells from multiple sclerosis patients. |
| title_sort | increased dna methylation of slfn12 in cd4 and cd8 t cells from multiple sclerosis patients |
| url | http://europepmc.org/articles/PMC6209300?pdf=render |
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