Genome-wide DNA methylation analysis of systemic lupus erythematosus reveals persistent hypomethylation of interferon genes and compositional changes to CD4+ T-cell populations.

Abstract:

:Systemic lupus erythematosus (SLE) is an autoimmune disease with known genetic, epigenetic, and environmental risk factors. To assess the role of DNA methylation in SLE, we collected CD4+ T-cells, CD19+ B-cells, and CD14+ monocytes from 49 SLE patients and 58 controls, and performed genome-wide DNA methylation analysis with Illumina Methylation 450 microarrays. We identified 166 CpGs in B-cells, 97 CpGs in monocytes, and 1,033 CpGs in T-cells with highly significant changes in DNA methylation levels (p < 1 × 10(-8)) among SLE patients. Common to all three cell-types were widespread and severe hypomethylation events near genes involved in interferon signaling (type I). These interferon-related changes were apparent in patients collected during active and quiescent stages of the disease, suggesting that epigenetically-mediated hypersensitivity to interferon persists beyond acute stages of the disease and is independent of circulating interferon levels. This interferon hypersensitivity was apparent in memory, naïve and regulatory T-cells, suggesting that this epigenetic state in lupus patients is established in progenitor cell populations. We also identified a widespread, but lower amplitude shift in methylation in CD4+ T-cells (> 16,000 CpGs at FDR < 1%) near genes involved in cell division and MAPK signaling. These cell type-specific effects are consistent with disease-specific changes in the composition of the CD4+ population and suggest that shifts in the proportion of CD4+ subtypes can be monitored at CpGs with subtype-specific DNA methylation patterns.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Absher DM,Li X,Waite LL,Gibson A,Roberts K,Edberg J,Chatham WW,Kimberly RP

doi

10.1371/journal.pgen.1003678

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

e1003678

issue

8

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-12-03165

journal_volume

9

pub_type

杂志文章
  • Extensive DNA end processing by exo1 and sgs1 inhibits break-induced replication.

    abstract::Homology-dependent repair of DNA double-strand breaks (DSBs) by gene conversion involves short tracts of DNA synthesis and limited loss of heterozygosity (LOH). For DSBs that present only one end, repair occurs by invasion into a homologous sequence followed by replication to the end of the chromosome resulting in ext...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1001007

    authors: Marrero VA,Symington LS

    更新日期:2010-07-08 00:00:00

  • Correction: Protein Poly(ADP-ribosyl)ation Regulates Arabidopsis Immune Gene Expression and Defense Responses.

    abstract::[This corrects the article DOI: 10.1371/journal.pgen.1004936.]. ...

    journal_title:PLoS genetics

    pub_type: 已发布勘误

    doi:10.1371/journal.pgen.1005294

    authors: Feng B,Liu C,de Oliveira MV,Intorne AC,Li B,Babilonia K,de Souza Filho GA,Shan L,He P

    更新日期:2016-09-09 00:00:00

  • A small set of conserved genes, including sp5 and Hox, are activated by Wnt signaling in the posterior of planarians and acoels.

    abstract::Wnt signaling regulates primary body axis formation across the Metazoa, with high Wnt signaling specifying posterior identity. Whether a common Wnt-driven transcriptional program accomplishes this broad role is poorly understood. We identified genes acutely affected after Wnt signaling inhibition in the posterior of t...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008401

    authors: Tewari AG,Owen JH,Petersen CP,Wagner DE,Reddien PW

    更新日期:2019-10-18 00:00:00

  • Mismatch repair balances leading and lagging strand DNA replication fidelity.

    abstract::The two DNA strands of the nuclear genome are replicated asymmetrically using three DNA polymerases, α, δ, and ε. Current evidence suggests that DNA polymerase ε (Pol ε) is the primary leading strand replicase, whereas Pols α and δ primarily perform lagging strand replication. The fact that these polymerases differ in...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003016

    authors: Lujan SA,Williams JS,Pursell ZF,Abdulovic-Cui AA,Clark AB,Nick McElhinny SA,Kunkel TA

    更新日期:2012-01-01 00:00:00

  • Unintentional miRNA ablation is a risk factor in gene knockout studies: a short report.

    abstract::One of the most powerful techniques for studying the function of a gene is to disrupt the expression of that gene using genetic engineering strategies such as targeted recombination or viral integration of gene trap cassettes. The tremendous utility of these tools was recognized this year with the awarding of the Nobe...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0040034

    authors: Osokine I,Hsu R,Loeb GB,McManus MT

    更新日期:2008-02-01 00:00:00

  • Mapping the fitness landscape of gene expression uncovers the cause of antagonism and sign epistasis between adaptive mutations.

    abstract::How do adapting populations navigate the tensions between the costs of gene expression and the benefits of gene products to optimize the levels of many genes at once? Here we combined independently-arising beneficial mutations that altered enzyme levels in the central metabolism of Methylobacterium extorquens to uncov...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004149

    authors: Chou HH,Delaney NF,Draghi JA,Marx CJ

    更新日期:2014-02-27 00:00:00

  • Repeated, selection-driven genome reduction of accessory genes in experimental populations.

    abstract::Genome reduction has been observed in many bacterial lineages that have adapted to specialized environments. The extreme genome degradation seen for obligate pathogens and symbionts appears to be dominated by genetic drift. In contrast, for free-living organisms with reduced genomes, the dominant force is proposed to ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002651

    authors: Lee MC,Marx CJ

    更新日期:2012-01-01 00:00:00

  • Cheating by exploitation of developmental prestalk patterning in Dictyostelium discoideum.

    abstract::The cooperative developmental system of the social amoeba Dictyostelium discoideum is susceptible to exploitation by cheaters-strains that make more than their fair share of spores in chimerae. Laboratory screens in Dictyostelium have shown that the genetic potential for facultative cheating is high, and field surveys...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000854

    authors: Khare A,Shaulsky G

    更新日期:2010-02-26 00:00:00

  • Recent acquisition of Helicobacter pylori by Baka pygmies.

    abstract::Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and m...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003775

    authors: Nell S,Eibach D,Montano V,Maady A,Nkwescheu A,Siri J,Elamin WF,Falush D,Linz B,Achtman M,Moodley Y,Suerbaum S

    更新日期:2013-01-01 00:00:00

  • Requirements for Pseudomonas aeruginosa acute burn and chronic surgical wound infection.

    abstract::Opportunistic infections caused by Pseudomonas aeruginosa can be acute or chronic. While acute infections often spread rapidly and can cause tissue damage and sepsis with high mortality rates, chronic infections can persist for weeks, months, or years in the face of intensive clinical intervention. Remarkably, this di...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004518

    authors: Turner KH,Everett J,Trivedi U,Rumbaugh KP,Whiteley M

    更新日期:2014-07-24 00:00:00

  • An essential role of variant histone H3.3 for ectomesenchyme potential of the cranial neural crest.

    abstract::The neural crest (NC) is a vertebrate-specific cell population that exhibits remarkable multipotency. Although derived from the neural plate border (NPB) ectoderm, cranial NC (CNC) cells contribute not only to the peripheral nervous system but also to the ectomesenchymal precursors of the head skeleton. To date, the d...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002938

    authors: Cox SG,Kim H,Garnett AT,Medeiros DM,An W,Crump JG

    更新日期:2012-09-01 00:00:00

  • Lipid-induced epigenomic changes in human macrophages identify a coronary artery disease-associated variant that regulates PPAP2B Expression through Altered C/EBP-beta binding.

    abstract::Genome-wide association studies (GWAS) have identified over 40 loci that affect risk of coronary artery disease (CAD) and the causal mechanisms at the majority of loci are unknown. Recent studies have suggested that many causal GWAS variants influence disease through altered transcriptional regulation in disease-relev...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005061

    authors: Reschen ME,Gaulton KJ,Lin D,Soilleux EJ,Morris AJ,Smyth SS,O'Callaghan CA

    更新日期:2015-04-02 00:00:00

  • Slit-Dependent Endocytic Trafficking of the Robo Receptor Is Required for Son of Sevenless Recruitment and Midline Axon Repulsion.

    abstract::Understanding how axon guidance receptors are activated by their extracellular ligands to regulate growth cone motility is critical to learning how proper wiring is established during development. Roundabout (Robo) is one such guidance receptor that mediates repulsion from its ligand Slit in both invertebrates and ver...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005402

    authors: Chance RK,Bashaw GJ

    更新日期:2015-09-03 00:00:00

  • A duplication CNV that conveys traits reciprocal to metabolic syndrome and protects against diet-induced obesity in mice and men.

    abstract::The functional contribution of CNV to human biology and disease pathophysiology has undergone limited exploration. Recent observations in humans indicate a tentative link between CNV and weight regulation. Smith-Magenis syndrome (SMS), manifesting obesity and hypercholesterolemia, results from a deletion CNV at 17p11....

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002713

    authors: Lacaria M,Saha P,Potocki L,Bi W,Yan J,Girirajan S,Burns B,Elsea S,Walz K,Chan L,Lupski JR,Gu W

    更新日期:2012-01-01 00:00:00

  • The FUN30 chromatin remodeler, Fft3, protects centromeric and subtelomeric domains from euchromatin formation.

    abstract::The chromosomes of eukaryotes are organized into structurally and functionally discrete domains. This implies the presence of insulator elements that separate adjacent domains, allowing them to maintain different chromatin structures. We show that the Fun30 chromatin remodeler, Fft3, is essential for maintaining a pro...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1001334

    authors: Strålfors A,Walfridsson J,Bhuiyan H,Ekwall K

    更新日期:2011-03-01 00:00:00

  • Introns regulate gene expression in Cryptococcus neoformans in a Pab2p dependent pathway.

    abstract::Most Cryptococccus neoformans genes are interrupted by introns, and alternative splicing occurs very often. In this study, we examined the influence of introns on C. neoformans gene expression. For most tested genes, elimination of introns greatly reduces mRNA accumulation. Strikingly, the number and the position of i...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003686

    authors: Goebels C,Thonn A,Gonzalez-Hilarion S,Rolland O,Moyrand F,Beilharz TH,Janbon G

    更新日期:2013-01-01 00:00:00

  • RAD50 is required for efficient initiation of resection and recombinational repair at random, gamma-induced double-strand break ends.

    abstract::Resection of DNA double-strand break (DSB) ends is generally considered a critical determinant in pathways of DSB repair and genome stability. Unlike for enzymatically induced site-specific DSBs, little is known about processing of random "dirty-ended" DSBs created by DNA damaging agents such as ionizing radiation. He...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000656

    authors: Westmoreland J,Ma W,Yan Y,Van Hulle K,Malkova A,Resnick MA

    更新日期:2009-09-01 00:00:00

  • ------Widespread conservation and lineage-specific diversification of genome-wide DNA methylation patterns across arthropods.

    abstract::Cytosine methylation is an ancient epigenetic modification yet its function and extent within genomes is highly variable across eukaryotes. In mammals, methylation controls transposable elements and regulates the promoters of genes. In insects, DNA methylation is generally restricted to a small subset of transcribed g...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008864

    authors: Lewis SH,Ross L,Bain SA,Pahita E,Smith SA,Cordaux R,Miska EA,Lenhard B,Jiggins FM,Sarkies P

    更新日期:2020-06-25 00:00:00

  • Directed Evolution Reveals Unexpected Epistatic Interactions That Alter Metabolic Regulation and Enable Anaerobic Xylose Use by Saccharomyces cerevisiae.

    abstract::The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006372

    authors: Sato TK,Tremaine M,Parreiras LS,Hebert AS,Myers KS,Higbee AJ,Sardi M,McIlwain SJ,Ong IM,Breuer RJ,Avanasi Narasimhan R,McGee MA,Dickinson Q,La Reau A,Xie D,Tian M,Reed JL,Zhang Y,Coon JJ,Hittinger CT,Gasch AP,La

    更新日期:2016-10-14 00:00:00

  • Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology.

    abstract::Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D ...

    journal_title:PLoS genetics

    pub_type: 杂志文章,meta分析

    doi:10.1371/journal.pgen.1006149

    authors: Shaffer JR,Orlova E,Lee MK,Leslie EJ,Raffensperger ZD,Heike CL,Cunningham ML,Hecht JT,Kau CH,Nidey NL,Moreno LM,Wehby GL,Murray JC,Laurie CA,Laurie CC,Cole J,Ferrara T,Santorico S,Klein O,Mio W,Feingold E,Hallgr

    更新日期:2016-08-25 00:00:00

  • Transcription facilitated genome-wide recruitment of topoisomerase I and DNA gyrase.

    abstract::Movement of the transcription machinery along a template alters DNA topology resulting in the accumulation of supercoils in DNA. The positive supercoils generated ahead of transcribing RNA polymerase (RNAP) and the negative supercoils accumulating behind impose severe topological constraints impeding transcription pro...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006754

    authors: Ahmed W,Sala C,Hegde SR,Jha RK,Cole ST,Nagaraja V

    更新日期:2017-05-02 00:00:00

  • The transcriptomes of two heritable cell types illuminate the circuit governing their differentiation.

    abstract::The differentiation of cells into distinct cell types, each of which is heritable for many generations, underlies many biological phenomena. White and opaque cells of the fungal pathogen Candida albicans are two such heritable cell types, each thought to be adapted to unique niches within their human host. To systemat...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1001070

    authors: Tuch BB,Mitrovich QM,Homann OR,Hernday AD,Monighetti CK,De La Vega FM,Johnson AD

    更新日期:2010-08-19 00:00:00

  • Molecular basis of hemoglobin adaptation in the high-flying bar-headed goose.

    abstract::During the adaptive evolution of a particular trait, some selectively fixed mutations may be directly causative and others may be purely compensatory. The relative contribution of these two classes of mutation to adaptive phenotypic evolution depends on the form and prevalence of mutational pleiotropy. To investigate ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007331

    authors: Natarajan C,Jendroszek A,Kumar A,Weber RE,Tame JRH,Fago A,Storz JF

    更新日期:2018-04-02 00:00:00

  • A discrete transition zone organizes the topological and regulatory autonomy of the adjacent tfap2c and bmp7 genes.

    abstract::Despite the well-documented role of remote enhancers in controlling developmental gene expression, the mechanisms that allocate enhancers to genes are poorly characterized. Here, we investigate the cis-regulatory organization of the locus containing the Tfap2c and Bmp7 genes in vivo, using a series of engineered chrom...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004897

    authors: Tsujimura T,Klein FA,Langenfeld K,Glaser J,Huber W,Spitz F

    更新日期:2015-01-08 00:00:00

  • A natural system of chromosome transfer in Yersinia pseudotuberculosis.

    abstract::The High Pathogenicity Island of Yersinia pseudotuberculosis IP32637 was previously shown to be horizontally transferable as part of a large chromosomal segment. We demonstrate here that at low temperature other chromosomal loci, as well as a non-mobilizable plasmid (pUC4K), are also transferable. This transfer, desig...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002529

    authors: Lesic B,Zouine M,Ducos-Galand M,Huon C,Rosso ML,Prévost MC,Mazel D,Carniel E

    更新日期:2012-01-01 00:00:00

  • RAN-binding protein 9 is involved in alternative splicing and is critical for male germ cell development and male fertility.

    abstract::As a member of the large Ran-binding protein family, Ran-binding protein 9 (RANBP9) has been suggested to play a critical role in diverse cellular functions in somatic cell lineages in vitro, and this is further supported by the neonatal lethality phenotype in Ranbp9 global knockout mice. However, the exact molecular ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004825

    authors: Bao J,Tang C,Li J,Zhang Y,Bhetwal BP,Zheng H,Yan W

    更新日期:2014-12-04 00:00:00

  • Role of exonic variation in chemokine receptor genes on AIDS: CCRL2 F167Y association with pneumocystis pneumonia.

    abstract::Chromosome 3p21-22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 and CCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We geno...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002328

    authors: An P,Li R,Wang JM,Yoshimura T,Takahashi M,Samudralal R,O'Brien SJ,Phair J,Goedert JJ,Kirk GD,Troyer JL,Sezgin E,Buchbinder SP,Donfield S,Nelson GW,Winkler CA

    更新日期:2011-10-01 00:00:00

  • Kinetochore-independent mechanisms of sister chromosome separation.

    abstract::Although kinetochores normally play a key role in sister chromatid separation and segregation, chromosome fragments lacking kinetochores (acentrics) can in some cases separate and segregate successfully. In Drosophila neuroblasts, acentric chromosomes undergo delayed, but otherwise normal sister separation, revealing ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1009304

    authors: Vicars H,Karg T,Warecki B,Bast I,Sullivan W

    更新日期:2021-01-29 00:00:00

  • Sustained activation of detoxification pathways promotes liver carcinogenesis in response to chronic bile acid-mediated damage.

    abstract::Chronic inflammation promotes oncogenic transformation and tumor progression. Many inflammatory agents also generate a toxic microenvironment, implying that adaptive mechanisms must be deployed for cells to survive and undergo transformation in such unfavorable contexts. A paradigmatic case is represented by cancers o...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007380

    authors: Collino A,Termanini A,Nicoli P,Diaferia G,Polletti S,Recordati C,Castiglioni V,Caruso D,Mitro N,Natoli G,Ghisletti S

    更新日期:2018-05-07 00:00:00

  • Fuzzy tandem repeats containing p53 response elements may define species-specific p53 target genes.

    abstract::Evolutionary forces that shape regulatory networks remain poorly understood. In mammals, the Rb pathway is a classic example of species-specific gene regulation, as a germline mutation in one Rb allele promotes retinoblastoma in humans, but not in mice. Here we show that p53 transactivates the Retinoblastoma-like 2 (R...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002731

    authors: Simeonova I,Lejour V,Bardot B,Bouarich-Bourimi R,Morin A,Fang M,Charbonnier L,Toledo F

    更新日期:2012-06-01 00:00:00