RFX1 downregulation contributes to TLR4 overexpression in CD14+ monocytes via epigenetic mechanisms in coronary artery disease.


BACKGROUND:Toll-like receptor 4 (TLR4) expression is increased in activated monocytes, which play a critical role in the pathogenesis of coronary artery disease (CAD). However, the mechanism remains unclear. Regulatory factor X1 (RFX1) is a critical transcription factor regulating epigenetic modifications. In this study, we investigated whether RFX1 and epigenetic modifications mediated by RFX1 contributed to the overexpression of TLR4 in activated monocytes. RESULTS:Compared with those of the controls, the mRNA and protein expression of RFX1 were downregulated and the mRNA expression of TLR4 was upregulated in CD14+ monocytes obtained from CAD patients and CD14+ monocytes obtained from healthy controls treated with low-density lipoprotein (LDL). The mRNA expression of RFX1 was negatively correlated with the mRNA expression of TLR4 in CD14+ monocytes. RFX1 knockdown led to the overexpression of TLR4 and the activation of CD14+ monocytes. In contrast, the overexpression of RFX1 inhibited TLR4 expression and the activation of CD14+ monocytes stimulated with LDL. Moreover, TLR4 was identified as a target gene of RFX1. The results indicated that RFX1 downregulation contributed to the decreased DNA methylation and histone H3 lysine 9 trimethylation and the increased H3 and H4 acetylation in the TLR4 promoter via the lack of recruitments of DNA methyltransferase 1 (DNMT1), histone deacetylase 1 (HDAC1), and histone-lysine N-methyltransferase SUV39H1 (SUV39H1), which were observed in CD14+ monocytes of CAD patients. CONCLUSIONS:Our results show that RFX1 expression deficiency leads to the overexpression of TLR4 and the activation of CD14+ monocytes in CAD patients by regulating DNA methylation and histone modifications, which highlights the vital role of RFX1 in the pathogenesis of CAD.


Clin Epigenetics


Clinical epigenetics


Du P,Gao K,Cao Y,Yang S,Wang Y,Guo R,Zhao M,Jia S




Has Abstract


2019-03-11 00:00:00














  • Exposure and fetal growth-associated miRNA alterations in the human placenta.

    abstract::Researchers have begun to examine epigenetic alterations in the placenta, making key advances in understanding the epigenetic regulatory mechanisms of the placenta that define underlying processes of human development and disease. Examining changes in microRNA (miRNA) expression associated with environmental exposures...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Maccani MA,Marsit CJ

    更新日期:2011-08-01 00:00:00

  • Genome-wide DNA methylation profiling of CD8+ T cells shows a distinct epigenetic signature to CD4+ T cells in multiple sclerosis patients.

    abstract:BACKGROUND:Multiple sclerosis (MS) is thought to be a T cell-mediated autoimmune disorder. MS pathogenesis is likely due to a genetic predisposition triggered by a variety of environmental factors. Epigenetics, particularly DNA methylation, provide a logical interface for environmental factors to influence the genome. ...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Maltby VE,Graves MC,Lea RA,Benton MC,Sanders KA,Tajouri L,Scott RJ,Lechner-Scott J

    更新日期:2015-11-05 00:00:00

  • Is Friedreich ataxia an epigenetic disorder?

    abstract:: Friedreich ataxia (FRDA) is a debilitating and frequently fatal neurological disorder that is recessively inherited. It belongs to the group of genetic disorders known as the Repeat Expansion Diseases, in which pathology arises from the deleterious consequences of the inheritance of a tandem repeat array whose repeat...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Kumari D,Usdin K

    更新日期:2012-01-30 00:00:00

  • The effects of olanzapine on genome-wide DNA methylation in the hippocampus and cerebellum.

    abstract:BACKGROUND:The mechanism of action of olanzapine in treating schizophrenia is not clear. This research reports the effects of a therapeutic equivalent treatment of olanzapine on DNA methylation in a rat model in vivo.Genome-wide DNA methylation was assessed using a MeDIP-chip analysis. All methylated DNA immunoprecipit...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Melka MG,Laufer BI,McDonald P,Castellani CA,Rajakumar N,O'Reilly R,Singh SM

    更新日期:2014-01-02 00:00:00

  • Identification and validation of SRY-box containing gene family member SOX30 methylation as a prognostic and predictive biomarker in myeloid malignancies.

    abstract:Background:Methylation-associated SOX family genes have been proved to be involved in multiple essential processes during carcinogenesis and act as potential biomarkers for cancer diagnosis, staging, prediction of prognosis, and monitoring of response to therapy. Herein, we revealed SOX30 methylation and its clinical i...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Zhou JD,Wang YX,Zhang TJ,Li XX,Gu Y,Zhang W,Ma JC,Lin J,Qian J

    更新日期:2018-07-05 00:00:00

  • Dietary intakes and biomarker patterns of folate, vitamin B6, and vitamin B12 can be associated with cognitive impairment by hypermethylation of redox-related genes NUDT15 and TXNRD1.

    abstract:BACKGROUND:B vitamins in the one-carbon metabolism pathway (folate, vitamin B6, and vitamin B12) have been implicated in DNA methylation, and their deficiency may contribute to cognitive decline through increased homocysteine (Hcy) levels and subsequent oxidative damage. The aim of this study was to investigate whether...

    journal_title:Clinical epigenetics

    pub_type: 临床试验,杂志文章


    authors: An Y,Feng L,Zhang X,Wang Y,Wang Y,Tao L,Qin Z,Xiao R

    更新日期:2019-10-11 00:00:00

  • Development of 5' LTR DNA methylation of latent HIV-1 provirus in cell line models and in long-term-infected individuals.

    abstract:BACKGROUND:Human immunodeficiency virus type 1 (HIV-1) latency represents the major barrier to virus eradication in infected individuals because cells harboring latent HIV-1 provirus are not affected by current antiretroviral therapy (ART). We previously demonstrated that DNA methylation of HIV-1 long terminal repeat (...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Trejbalová K,Kovářová D,Blažková J,Machala L,Jilich D,Weber J,Kučerová D,Vencálek O,Hirsch I,Hejnar J

    更新日期:2016-02-19 00:00:00

  • Pulmonary microRNA profiling: implications in upper lobe predominant lung disease.

    abstract:BACKGROUND:Numerous pulmonary diseases manifest with upper lobe predominance including cystic fibrosis, smoking-related chronic obstructive pulmonary disease, and tuberculosis. Zonal hypoxia, characteristic of these pulmonary maladies, and oxygen stress in general is known to exert profound effects on various important...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Armstrong DA,Nymon AB,Ringelberg CS,Lesseur C,Hazlett HF,Howard L,Marsit CJ,Ashare A

    更新日期:2017-05-30 00:00:00

  • Overall and sex-specific associations between methylation of the ABCG1 and APOE genes and ischemic stroke or other atherosclerosis-related traits in a sibling study of Chinese population.

    abstract:BACKGROUND:Identifying subjects with a high risk of ischemic stroke is fundamental for prevention of the disease. Both genetic and environmental risk factors contribute to ischemic stroke, but the underlying epigenetic mechanisms which mediate genetic and environmental risk effects are not fully understood. The aim of ...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Qin X,Li J,Wu T,Wu Y,Tang X,Gao P,Li L,Wang M,Wu Y,Wang X,Chen D,Hu Y

    更新日期:2019-12-10 00:00:00

  • Maternal B vitamins: effects on offspring weight and DNA methylation at genomically imprinted domains.

    abstract:BACKGROUND:Inadequate maternal nutrition during early fetal development can create permanent alterations in the offspring, leading to poor health outcomes. While nutrients involved in one-carbon cycle metabolism are important to fetal growth, associations with specific nutrients remain inconsistent. This study estimate...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: McCullough LE,Miller EE,Mendez MA,Murtha AP,Murphy SK,Hoyo C

    更新日期:2016-01-22 00:00:00

  • Suffocating cancer: hypoxia-associated epimutations as targets for cancer therapy.

    abstract:: Lower than normal levels of oxygen (hypoxia) is a hallmark of all solid tumours rendering them frequently resistant to both radiotherapy and chemotherapy regimes. Furthermore, tumour hypoxia and activation of the hypoxia inducible factor (HIF) transcriptional pathway is associated with poorer prognosis. Driven by bot...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Thirlwell C,Schulz L,Dibra H,Beck S

    更新日期:2011-12-05 00:00:00

  • Two independent epigenetic biomarkers predict survival in neuroblastoma.

    abstract:BACKGROUND:Neuroblastoma (NB) is the most common extracranial pediatric solid tumor with a highly variable clinical course, ranging from spontaneous regression to life-threatening disease. Survival rates for high-risk NB patients remain disappointingly low despite multimodal treatment. Thus, there is an urgent clinical...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Yáñez Y,Grau E,Rodríguez-Cortez VC,Hervás D,Vidal E,Noguera R,Hernández M,Segura V,Cañete A,Conesa A,Font de Mora J,Castel V

    更新日期:2015-02-27 00:00:00

  • Epigenomic profiling of prostate cancer identifies differentially methylated genes in TMPRSS2:ERG fusion-positive versus fusion-negative tumors.

    abstract:BACKGROUND:About half of all prostate cancers harbor the TMPRSS2:ERG (T2E) gene fusion. While T2E-positive and T2E-negative tumors represent specific molecular subtypes of prostate cancer (PCa), previous studies have not yet comprehensively investigated how these tumor subtypes differ at the epigenetic level. We theref...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Geybels MS,Alumkal JJ,Luedeke M,Rinckleb A,Zhao S,Shui IM,Bibikova M,Klotzle B,van den Brandt PA,Ostrander EA,Fan JB,Feng Z,Maier C,Stanford JL

    更新日期:2015-12-12 00:00:00

  • Epigenetic stratification of head and neck cancer survivors reveals differences in lycopene levels, alcohol consumption, and methylation of immune regulatory genes.

    abstract:BACKGROUND:Inflammation has been associated with higher rates of recurrence and mortality in head and neck cancer (HNC). While the biological mechanisms predisposing patients to heightened inflammatory states remain largely unknown, DNA methylation has been proposed to reflect systemic inflammation. In this analysis, w...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Moody L,Crowder SL,Fruge AD,Locher JL,Demark-Wahnefried W,Rogers LQ,Delk-Licata A,Carroll WR,Spencer SA,Black M,Erdman JW Jr,Chen H,Pan YX,Arthur AE

    更新日期:2020-09-11 00:00:00

  • Analysis of two birth tissues provides new insights into the epigenetic landscape of neonates born preterm.

    abstract:BACKGROUND:Preterm birth (PTB), defined as child birth before completion of 37 weeks of gestation, is a major challenge in perinatal health care and can bear long-term medical and financial burden. Over a million children die each year due to PTB complications, and those who survive can face developmental delays. Unfor...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Wu Y,Lin X,Lim IY,Chen L,Teh AL,MacIsaac JL,Tan KH,Kobor MS,Chong YS,Gluckman PD,Karnani N

    更新日期:2019-02-11 00:00:00

  • TWIST1 DNA methylation is a cell marker of airway and parenchymal lung fibroblasts that are differentially methylated in asthma.

    abstract:BACKGROUND:Mesenchymal fibroblasts are ubiquitous cells that maintain the extracellular matrix of organs. Within the lung, airway and parenchymal fibroblasts are crucial for lung development and are altered with disease, but it has been difficult to understand their roles due to the lack of distinct molecular markers. ...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Clifford RL,Yang CX,Fishbane N,Patel J,MacIsaac JL,McEwen LM,May ST,Castellanos-Uribe M,Nair P,Obeidat M,Kobor MS,Knox AJ,Hackett TL

    更新日期:2020-10-02 00:00:00

  • Alternative methylation of intron motifs is associated with cancer-related gene expression in both canine mammary tumor and human breast cancer.

    abstract:BACKGROUND:Canine mammary tumor (CMT) has long been considered as a good animal model for human breast cancer (HBC) due to their pathological and biological similarities. However, only a few aspects of the epigenome have been explored in both HBC and CMT. Moreover, DNA methylation studies have mainly been limited to th...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Nam AR,Lee KH,Hwang HJ,Schabort JJ,An JH,Won SH,Cho JY

    更新日期:2020-07-21 00:00:00

  • The neuropeptide genes SST, TAC1, HCRT, NPY, and GAL are powerful epigenetic biomarkers in head and neck cancer: a site-specific analysis.

    abstract:Background:Staging and pathological grading systems are convenient but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). Identifying biomarkers for HNSCC that will progress and cause death is a critical research area, particularly if the biomarker can be linked to selection of patient...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Misawa K,Mima M,Imai A,Mochizuki D,Misawa Y,Endo S,Ishikawa R,Kanazawa T,Mineta H

    更新日期:2018-04-11 00:00:00

  • Comparative DNA methylomic analyses reveal potential origins of novel epigenetic biomarkers of insulin resistance in monocytes from virally suppressed HIV-infected adults.

    abstract:BACKGROUND:Compared to healthy individuals, those with stably repressed HIV experience a higher risk of developing insulin resistance, a hallmark of pre-diabetes and a major determinant for cardiometabolic diseases. Although epigenetic processes, including in particular DNA methylation, appear to be dysregulated in ind...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Dye CK,Corley MJ,Li D,Khadka VS,Mitchell BI,Sultana R,Lum-Jones A,Shikuma CM,Ndhlovu LC,Maunakea AK

    更新日期:2019-06-28 00:00:00

  • Racial differences in IGF1 methylation and birth weight.

    abstract:BACKGROUND:The birth weight of Black neonates in the United States is consistently smaller than that of their White counterparts. Epigenetic differences between the races may be involved in such disparities. The goal of these analyses was to model the role of IGF1 methylation in mediating the association between race a...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Straughen JK,Sipahi L,Uddin M,Misra DP,Misra VK

    更新日期:2015-04-21 00:00:00

  • The role of microRNA-1246 in the regulation of B cell activation and the pathogenesis of systemic lupus erythematosus.

    abstract:BACKGROUND:The pathogenesis of systemic lupus erythematosus (SLE) has not yet been completely elucidated. One of the hallmarks of SLE is the production of autoantibodies by uncontrolled over-activated B cells. Early B cell factor 1 (EBF1) contributes to the development, activation, and proliferation of B cells through ...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Luo S,Liu Y,Liang G,Zhao M,Wu H,Liang Y,Qiu X,Tan Y,Dai Y,Yung S,Chan TM,Lu Q

    更新日期:2015-03-14 00:00:00

  • Individual epigenetic status of the pathogenic D4Z4 macrosatellite correlates with disease in facioscapulohumeral muscular dystrophy.

    abstract:BACKGROUND:Both forms of facioscapulohumeral muscular dystrophy (FSHD) are associated with aberrant epigenetic regulation of the chromosome 4q35 D4Z4 macrosatellite. Chromatin changes due to large deletions of heterochromatin (FSHD1) or mutations in chromatin regulatory proteins (FSHD2) lead to relaxation of epigenetic...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Jones TI,King OD,Himeda CL,Homma S,Chen JC,Beermann ML,Yan C,Emerson CP Jr,Miller JB,Wagner KR,Jones PL

    更新日期:2015-03-29 00:00:00

  • Characterisation of DNA methylation changes in EBF3 and TBC1D16 associated with tumour progression and metastasis in multiple cancer types.

    abstract:BACKGROUND:Characteristic DNA methylation differences have been identified between primary and metastatic melanomas at EBF3 and/or TBC1D16 gene loci. To further evaluate whether these epigenetic changes may act more generally as drivers of tumour onset and metastasis, we have investigated DNA methylation changes involv...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Rodger EJ,Chatterjee A,Stockwell PA,Eccles MR

    更新日期:2019-08-05 00:00:00

  • Gene domain-specific DNA methylation episignatures highlight distinct molecular entities of ADNP syndrome.

    abstract:BACKGROUND:ADNP syndrome is a rare Mendelian disorder characterized by global developmental delay, intellectual disability, and autism. It is caused by truncating mutations in ADNP, which is involved in chromatin regulation. We hypothesized that the disruption of chromatin regulation might result in specific DNA methyl...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Bend EG,Aref-Eshghi E,Everman DB,Rogers RC,Cathey SS,Prijoles EJ,Lyons MJ,Davis H,Clarkson K,Gripp KW,Li D,Bhoj E,Zackai E,Mark P,Hakonarson H,Demmer LA,Levy MA,Kerkhof J,Stuart A,Rodenhiser D,Friez MJ,Stevenson

    更新日期:2019-04-27 00:00:00

  • DNA methylation signature of interleukin 1 receptor type II in asthma.

    abstract::Interleukin 1 and its receptors are associated with allergic diseases such as asthma. In the present study, we measured DNA methylation at the IL1R1 and IL1R2 gene loci and assessed for associations with asthma-related phenotypes and gene expressions. We found that asthmatic and atopic individuals have higher IL1R2 pr...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Gagné-Ouellet V,Guay SP,Boucher-Lafleur AM,Bouchard L,Laprise C

    更新日期:2015-08-05 00:00:00

  • Smoking induces coordinated DNA methylation and gene expression changes in adipose tissue with consequences for metabolic health.

    abstract:BACKGROUND:Tobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but the extent to which these changes are widespread to metabolically relevant tissues, and impact gene expression or metabolic hea...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Tsai PC,Glastonbury CA,Eliot MN,Bollepalli S,Yet I,Castillo-Fernandez JE,Carnero-Montoro E,Hardiman T,Martin TC,Vickers A,Mangino M,Ward K,Pietiläinen KH,Deloukas P,Spector TD,Viñuela A,Loucks EB,Ollikainen M,Kelsey K

    更新日期:2018-10-20 00:00:00

  • SLCO4C1 promoter methylation is a potential biomarker for prognosis associated with biochemical recurrence-free survival after radical prostatectomy.

    abstract:BACKGROUND:Prostate cancer (PC) is a commonly diagnosed malignancy in males, especially in the western hemisphere. The extensive use of multiple biomarkers plays an important role in the diagnosis and prognosis of PC. However, the accuracy of biomarkers for PC prognosis needs to be urgently improved. This study aimed t...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Li X,Zhang W,Song J,Zhang X,Ran L,He Y

    更新日期:2019-07-09 00:00:00

  • Combined inhibition of BET proteins and class I HDACs synergistically induces apoptosis in urothelial carcinoma cell lines.

    abstract:Background:New efficient therapies for urothelial carcinoma (UC) are urgently required. Small-molecule drugs targeting chromatin regulators are reasonable candidates because these regulators are frequently mutated or deregulated in UC. Indeed, in previous work, Romidepsin, which targets class I histone deacetylases (HD...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Hölscher AS,Schulz WA,Pinkerneil M,Niegisch G,Hoffmann MJ

    更新日期:2018-01-04 00:00:00

  • Genome-wide DNA methylation profiles of low- and high-grade adenoma reveals potential biomarkers for early detection of colorectal carcinoma.

    abstract:BACKGROUND:Abnormal DNA methylation is a hallmark of human cancers and may be a promising biomarker for early diagnosis of human cancers. However, the majority of DNA methylation biomarkers that have been identified are based on the hypothesis that early differential methylation regions (DMRs) are maintained throughout...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Fan J,Li J,Guo S,Tao C,Zhang H,Wang W,Zhang Y,Zhang D,Ding S,Zeng C

    更新日期:2020-04-21 00:00:00

  • DNA methylation and repressive histones in the promoters of PD-1, CTLA-4, TIM-3, LAG-3, TIGIT, PD-L1, and galectin-9 genes in human colorectal cancer.

    abstract:BACKGROUND:Colorectal cancer (CRC) is the third most commonly diagnosed human malignancy worldwide. Upregulation of inhibitory immune checkpoints by tumor-infiltrating immune cells (TIICs) or their ligands by tumor cells leads to tumor evasion from host immunosurveillance. Changes in DNA methylation pattern and enrichm...

    journal_title:Clinical epigenetics

    pub_type: 杂志文章


    authors: Sasidharan Nair V,Toor SM,Taha RZ,Shaath H,Elkord E

    更新日期:2018-08-06 00:00:00