DNA methylation and gene expression signatures are associated with ataxia-telangiectasia phenotype.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
04 05 2020
04 05 2020
Historique:
received:
19
02
2020
accepted:
13
04
2020
entrez:
6
5
2020
pubmed:
6
5
2020
medline:
25
11
2020
Statut:
epublish
Résumé
People with ataxia-telangiectasia (A-T) display phenotypic variability with regard to progression of immunodeficiency, sino-pulmonary disease, and neurologic decline. To determine the association between differential gene expression, epigenetic state, and phenotypic variation among people with A-T, we performed transcriptional and genome-wide DNA methylation profiling in patients with mild and classic A-T progression as well as healthy controls. RNA and genomic DNA were isolated from peripheral blood mononuclear cells for transcriptional and DNA methylation profiling with RNA-sequencing and modified reduced representation bisulfite sequencing, respectively. We identified 555 genes that were differentially expressed among the control, mild A-T, and classic A-T groups. Genome-wide DNA methylation profiling revealed differential promoter methylation in cis with 146 of these differentially expressed genes. Functional enrichment analysis identified significant enrichment in immune, growth, and apoptotic pathways among the methylation-regulated genes. Regardless of clinical phenotype, all A-T participants exhibited downregulation of critical genes involved in B cell function (PAX5, CD79A, CD22, and FCRL1) and upregulation of several genes associated with senescence and malignancy, including SERPINE1. These findings indicate that gene expression differences may be associated with phenotypic variability and suggest that DNA methylation regulates expression of critical immune response genes in people with A-T.
Identifiants
pubmed: 32366930
doi: 10.1038/s41598-020-64514-2
pii: 10.1038/s41598-020-64514-2
pmc: PMC7198504
doi:
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7479Subventions
Organisme : NHLBI NIH HHS
ID : K08 HL128867
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL146943
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL114800
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149883
Pays : United States
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