Cell-specific epigenome-wide DNA methylation profile in long-term cultured minor salivary gland epithelial cells from patients with Sjögren's syndrome

Charras, Amandine; Konsta, Orsia D; Dantec, Christelle Le; Bagacean, Cristina; Kapsogeorgou, Efstathia K.; Tzioufas, Athanasios G.; Pers, Jacques‐Olivier; Bordron, Anne; Renaudineau, Yves

doi:10.1136/annrheumdis-2016-210167

Cited by 47 publications

(42 citation statements)

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“…Therefore, upregulation of XIST and polycomb repressor complex genes determined in our analysis likely occurs in SGECs. In addition, previous genomewide methylation studies of lymphocytes from patients with SS did not report differential methylation of X‐chromosome genes, while the study by Charras et al., () using cultured SS SGECs showed differential methylation of seven genes that are differentially expressed in SS SGs ((ACSL4, BCOR, IL2RG, MAGEB1, MAGEE2, RP2, SMARCA1; Figure ); Imgenberg‐Kreuz et al., ; Miceli‐Richard et al., ). However, the study by Imgenberg‐Kreuz et al.…”

Section: Discussionmentioning

confidence: 91%

“…First, genes belonging to Polycomb Repressor Complexes 1 and 2 (PRC1/2) with a FC AVG of ≥1.50 in the three SG datasets were included. Second, the methylation status of X‐chromosome gene, transcription factors, and PRC1/2 genes was determined based on published data obtained from long‐term cultured SGECs isolated from patients with SS and controls (Charras et al., ). To compare SS PBMC gene expression to SS SG gene expression of candidate genes, the GEO dataset was used.…”

Section: Methodsmentioning

confidence: 99%

“…T A B L E 2 (Continued) obtained from long-term cultured SGECs isolated from patients with SS and controls (Charras et al, 2017). To compare SS PBMC gene expression to SS SG gene expression of candidate genes, the GEO dataset GSE51092 was used.…”

Section: Methodsmentioning

confidence: 99%

“…Methylation status of the X-chromosome, PRC1/2, and TF genes was determined to account for known epigenetic modifications which possibly intervene in their expression. Three TFs, previously shown to present aberrant methylation patterns within cultured SGECs or the labial SG of SS patients, were identified as follows: IRF8**, RELA** (hypermethylated) (Charras et al, 2017), and SPI1 # (hypomethylated) (Cole et al, 2016) (Figure 2). All three TFs are involved in immune cell signaling (Li & Verma, 2002;Goetz & Baldwin, 2008;Kanno, Levi, Tamura & Ozato, 2005;UniProt, 2017).…”

Section: Molecular Network: Interactions Between X-chromosome Genesmentioning

confidence: 98%

“…These genes were cross-referenced with the online tool "transcriptional regulatory relationships unraveled by sentence-based text-mining" (TRRUST) to find upregulated TFs (FC AVG ≥ 1.20) that activate their corresponding X-chromosome gene. Following the identification of these TFs and X-chromosome gene relationships, the methylation status of each gene was determined using two separate SS SG methylation datasets (Charras et al, 2017;Cole et al, 2016). Bold indicates the gene has been implicated in autoimmunity (Bianchi et al 2012).…”

Section: Molecular Network: Interactions Between X-chromosome Genesmentioning

confidence: 99%

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Sjögren's syndrome X‐chromosome dose effect: An epigenetic perspective

2018

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Sjögren's syndrome (SS) is a chronic autoimmune disease affecting exocrine glands leading to mouth and eyes dryness. The extent to which epigenetic DNA methylation changes are responsible for an X-chromosome dose effect has yet to be determined. Our objectives were to (i) describe how epigenetic DNA methylation changes could explain an X-chromosome dose effect in SS for women with normal 46,XX genotype and (ii) determine the relevant relationships to this dose effect, between X-linked genes, genes controlling X-chromosome inactivation (XCI) and genes encoding associated transcription factors, all of which are differentially expressed and/or differentially methylated in the salivary glands of patients with SS. We identified 58 upregulated X-chromosome genes, including 22 genes previously shown to escape XCI, based on the analysis of SS patient salivary gland GEO2R gene expression datasets. Moreover, we found XIST and its cis regulators RLIM, FTX, and CHIC1, and polycomb repressor genes of the PRC1/2 complexes to be upregulated. Many of the X-chromosome genes implicated in SS pathogenesis can be regulated by transcription factors which we found to be overexpressed and/or differentially methylated in patients with SS. Determination of the mechanisms underlying methylation-dependent gene expression and impaired XCI is needed to further elucidate the etiopathogenesis of SS.

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Section: Discussionmentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%