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DNMT1 (DNA methyltransferase 1) is the predominant member of the DNMT family and the most abundant DNMT in various cell types. It functions as a maintenance DNMT and is involved in various diseases, including cancer and nervous system diseases. Programmed cell death (PCD) is a fundamental mechanism that regulates cell proliferation and maintains the development and homeostasis of multicellular organisms. DNMT1 plays a regulatory role in various types of PCD, including apoptosis, autophagy, necroptosis, ferroptosis, and others. DNMT1 is closely associated with the development of various diseases by regulating key genes and pathways involved in PCD, including caspase 3/7 activities in apoptosis, Beclin 1, LC3, and some autophagy-related proteins in autophagy, glutathione peroxidase 4 (GPX4) and nuclear receptor coactivator 4 (NCOA4) in ferroptosis, and receptor-interacting protein kinase 1-receptor-interacting protein kinase 3-mixed lineage kinase domain-like protein (RIPK1-RIPK3-MLKL) in necroptosis. Our study summarizes the regulatory relationship between DNMT1 and different types of PCD in various diseases and discusses the potential of DNMT1 as a common regulatory hub in multiple types of PCD, offering a perspective for therapeutic approaches in disease.

Dysferlin (DYSF) has drawn much attention due to its involvement in dysferlinopathy and was reported to affect monocyte functions in recent studies. However, the role of DYSF in the pathogenesis of atherosclerotic cardiovascular diseases (ASCVD) and the regulation mechanism of DYSF expression have not been fully studied. In this study, Gene Expression Omnibus (GEO) database and epigenome-wide association study (EWAS) literatures were searched to find the DNA methylation-driven genes (including DYSF) of ASCVD. The hub genes related to DYSF were also identified through weighted correlation network analysis (WGCNA). Regulation of DYSF expression through its promoter methylation status was verified using peripheral blood leucocytes (PBLs) from ASCVD patients and normal controls, and experiments on THP1 cells and Apoe -/- mice. Similarly, the expressions of DYSF related hub genes, mainly contained SELL, STAT3 and TMX1, were also validated. DYSF functions were then evaluated by phagocytosis, transwell and adhesion assays in DYSF knock-down and overexpressed THP1 cells. The results showed that DYSF promoter hypermethylation up-regulated its expression in clinical samples, THP1 cells and Apoe -/- mice, confirming DYSF as a DNA methylation-driven gene. The combination of DYSF expression and methylation status in PBLs had a considerable prediction value for ASCVD. Besides, DYSF could enhance the phagocytosis, migration and adhesion ability of THP1 cells. Among DYSF related hub genes, SELL was proven to be the downstream target of DYSF by wet experiments. In conclusion, DYSF promoter hypermethylation upregulated its expression and promoted monocytes activation, which further participated in the pathogenesis of ASCVD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: Heart failure (HF) is a progressive disease with recurrent hospitalizations and high mortality. However, the mechanisms underlying HF remain unclear. The present study aimed to explore the regulatory mechanism of histone deacetylase 3 (HDAC3) and DNA methyltransferase 1 (DNMT1)/Src homology domain 2-containing tyrosine phosphatase-1 (SHP-1) axis in HF., Methods: The HF rat models and hypertrophy cell models were established. The characteristic parameters of the heart were detected by echocardiography. A multichannel physiological signal acquisition system was used to detect the hemodynamic parameters. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of HDAC3, DNMT1, and SHP-1 mRNAs, while Western blot was applied to analyze the expression of proteins. Masson staining was used to analyze the degree of collagen fiber infiltration. TdT-mediated DUTP nick end labeling (TUNEL) staining was performed to analyze the apoptosis of myocardial tissue cells. Co-immunoprecipitation (co-IP) was conducted to study the interaction between HDAC3 and DNMT1. Flow cytometry was used to analyze the apoptosis., Key Findings: HDAC3 and DNMT1 were highly expressed in HF rat and hypertrophy cell models. HDAC3 modified DNMT1 through deacetylation to inhibit ubiquitination-mediated degradation, which promoted the expression of DNMT1. DNMT1 inhibited SHP-1 expression via methylation in the promoter region. In summary, HDAC3 modified DNMT1 by deacetylation to suppress SHP-1 expression, which in turn led to the development of cardiomyocyte hypertrophy-induced HF., Significance: This study provided potential therapeutic targets for HF treatment., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

DNA methyltransferase 1 (Dnmt1) is crucial for cell maintenance and preferentially methylates hemimethylated DNA. Recently, a study revealed that Dnmt1 is timely and site-specifically activated by several types of two-mono-ubiquitinated histone H3 tails (H3Ts). However, the molecular mechanism of Dnmt1 activation has not yet been determined, in addition to the role of H3T. Based on experimental data, two-mono-ubiquitinated H3Ts activate Dnmt1 by binding, with different binding affinities. In contrast, ubiquitin molecules unlinked with H3T do not bind to Dnmt1. Despite the existence of experimental data, it is unclear why the binding affinities for Dnmt1 are different. To obtain new insights into the activation mechanism of Dnmt1, we performed all-atom molecular dynamics (MD) simulations on three systems: (1) K14/K18, (2) K14/K23 mono-ubiquitinated H3Ts, and (3) two ubiquitin molecules unlinked with H3T. As an analysis of our MD trajectories, these ubiquitylation patterns modulated ubiquitin-ubiquitin intermolecular interactions. More specifically, the intermolecular contacts between a pair of ubiquitin molecules linked with H3T became weak in the presence of H3T, indicating that H3T makes a cleft between them to inhibit their intermolecular interactions. For these three systems, the intermolecular interactions between the ubiquitin molecules calculated by our MD simulations are in good agreement with the binding affinities for Dnmt1 experimentally measured in a previous study. Therefore, we conclude that H3T acts as a spacer to inhibit ubiquitin-ubiquitin intermolecular interactions, enhancing binding to Dnmt1., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Research Question: What is the mechanism of hypermethylation of runt-related transcription factor 3 (RUNX3) in the eutopic endometrium of endometriosis as biomarker in the malignant transformation of endometriosis?, Design: Methylation-specific polymerase chain reaction was used to analyse the methylation status of RUNX3 in endometriosis-associated ovarian cancer (EAOC). Primary eutopic endometrial stromal cells (ESC) were isolated from the uteri of patients with ovarian endometriosis. After RUNX3 knockdown by RNA interference technology or ESC treated with oestradiol, the proliferation and invasion ability were evaluated in ESC by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and transwell assays., Results: The frequency of methylation of RUNX3 in neoplastic tissue in the EAOC group was significantly higher than that in the ectopic endometrium of the endometriosis group (P < 0.001), and the frequency of methylation of RUNX3 in the eutopic endometrium of the EAOC group was significantly higher than that in the endometriosis group (P < 0.001). However, there was no significant difference in the eutopic endometrium when compared between the endometriosis group and the control endometrium group (P = 0.233). Silencing RUNX3 promoted the proliferation and invasion of ESC (P < 0.001 and P < 0.001). Following intervention with oestrogen, it was observed that the oestradiol group showed higher levels of RUNX3 methylation (P < 0.001) and DNA methyltransferase 1 (DNMT1) mRNA and protein expression (P < 0.001 and P < 0.001), and lower RUNX3 mRNA and protein expression when compared with the ESC group (P < 0.001 and P < 0.001)., Conclusion: This study demonstrated that hypermethylation of the RUNX3 was related to the malignant transformation of endometriosis and that this process was related to corresponding changes in the eutopic endometrium. Furthermore, the 'oestrogen-DNMT1' signalling pathway may induce the hypermethylation of RUNX3 to promote the malignant transformation of endometriosis., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Excessive binge alcohol intake is a common drinking pattern in humans, especially during holidays. Cessation of the binge drinking often leads to aberrant withdrawal behaviors, as well as serious heart rhythm abnormalities (clinically diagnosed as Holiday Heart Syndrome (HHS)). In our HHS mouse model with well-characterized binge alcohol withdrawal (BAW)-induced heart phenotypes, BAW leads to anxiety-like behaviors and cognitive impairment. We have previously reported that stress-activated c-Jun NH(2)-terminal kinase (JNK) plays a causal role in BAW-induced heart phenotypes. In the HHS brain, we found that activation of JNK2 (but not JNK1 and JNK3) in the prefrontal cortex (PFC), but not hippocampus and amygdala, led to anxiety-like behaviors and impaired cognition. DNA methylation mediated by a crucial DNA methylation enzyme, DNA methyltransferase1 (DNMT1), is known to be critical in alcohol-associated behavioral deficits. In HHS mice, JNK2 in the PFC (but not hippocampus and amygdala) causally enhanced total genomic DNA methylation via increased DNMT1 expression, which was regulated by enhanced binding of JNK downstream transcriptional factor c-JUN to the DNMT1 promoter. JNK2-specific inhibition either by an inhibitor JNK2I or JNK2 knockout completely offset c-JUN-regulated DNMT1 upregulation and restored the level of DNA methylation in HHS PFC to the baseline levels seen in sham controls. Strikingly, either JNK2-specific inhibition or genetic JNK2 depletion or DNMT1 inhibition (by an inhibitor 5-Azacytidine) completely abolished BAW-evoked behavioral deficits. In conclusion, our studies revealed a novel mechanism by which JNK2 drives BAW-evoked behavioral deficits through a DNMT1-regulated DNA hypermethylation. JNK2 could be a novel therapeutic target for alcohol withdrawal treatment and/or prevention., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

DNA methyltransferase 1 (DNMT1) is one of the most essential proteins in propagating DNA methylation patterns during replication. Developing methods to assess the expression level of DNMT1 will enable study of gene methylation abnormalities. Thus, a series of fluorescein-conjugated RG108 derivatives were designed and synthesized in the current study. The affinity of the derivatives with DNMT1 was evaluated using surface plasmon resonance. Permeability of the derivatives through the cytomembrane and nuclear envelope was evaluated via confocal imaging. Probe 8a was found to compete with RG108 binding to DNMT1 in the nucleus of HeLa cells, suggesting that probe 8a and RG108 share the same binding site. A HeLa cell model with 4.05-fold overexpression of DNMT1 was constructed and used to evaluate probe 8a. Probe 8a was found to be significantly increased in the nucleus of DNMT1 overexpressing cells. These results indicate that fluorescent probes derived from RG108 have the potential to be used for evaluating the expression level of DNMT1 in living cells., (Copyright © 2020 Elsevier Inc. All rights reserved.)

DNA methylation is an epigenetic modification that regulates gene transcription. DNA methyltransferase 1 (DNMT1) plays an important role in DNA methylation. However, the involvement of DNMT1 and DNA methylation in the pathogenesis of atopic dermatitis (AD) remains unclear. In this study, microarray analysis revealed that peripheral blood mononuclear cells of AD patients with low DNMT1 expression (DNMT1-low) highly expressed dendritic cell (DC) activation-related genes. Also, DNMT1-low AD patients exhibited a higher itch score compared to AD patients with high DNMT1 expression (DNMT1-high). By using an AD-like mouse model induced by the application of Dermatophagoides farinae body ointment, we found that Dnmt1 expression was decreased, while the expression of C-C chemokine receptor type 7 (Ccr7) was upregulated in mouse skin DCs. Furthermore, mice exposed to social defeat stress exhibited Dnmt1 downregulation and Ccr7 upregulation in skin DCs. Additionally, dermatitis and itch-related scratching behavior were exacerbated in AD mice exposed to stress. The relationship between low DNMT1 and itch induction was found in both human AD patients and AD mice. In mouse bone marrow-derived DCs, Ccr7 expression was inhibited by 5-aza-2-deoxycytidine, a methylation inhibitor. Furthermore, in mouse skin DCs, methylation of CpG sites in Ccr7 was modified by either AD induction or social defeat stress. Collectively, these findings suggest that social defeat stress exacerbates AD pathology through Dnmt1 downregulation and Ccr7 upregulation in mouse skin DCs. The data also suggest a role of DNMT1 downregulation in the exacerbation of AD pathology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The BCL6 proto-oncogene encodes a transcriptional repressor, which is required for germinal centers (GCs) formation and lymphomagenesis. Previous studies have been reported that the constitutive expression of BCL6 leads to diffuse large B cell lymphoma (DLBCL) through activation-induced cytidine deaminase (AID) mediated chromosomal translocations and mutations. However, other DLBCLs (45%) without structural variants were characterized by abnormally high level of BCL6 expression through an unknown mechanism. Herein, we report that deficiency in AID or methyltransferase 1 (DNMT1) triggers high level of BCL6 expression. AID-DNMT1 complex binds to -0.4 kb -0 kb region of BCL6 promoter and contributes to generate BCL6 methylation which results in inhibition of BCL6 expression. The proteasome pathway inhibitor MG132 induces accumulation of AID and DNMT1, causes decreased BCL6 expression, and leads to cell apoptosis and tumor growth inhibition in DLBCL cell xenograft mice. These findings propose mechanistic insight into an alternative cofactor role of AID in assisting DNMT1 to maintain BCL6 methylation, thus suppress BCL6 transcription in DLBCL. This novel mechanism will provide a new drug selection in the therapeutic approach to DLBCL in the future., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

DNA methylation has been implicated in the pathogenesis of diabetic kidney disease (DKD), but the underlying mechanisms remain unclear. In this study, we tested the hypothesis that aberrant DNA methylation in peripheral immune cells contributes to DKD progression. We showed that levels of DNA methyltransferase 1 (DNMT1), a key enzyme for DNA methylation, were increased along with inflammatory activity of peripheral blood mononuclear cells in DKD patients. Inhibition of DNMT1 with 5-aza-2'-deoxycytidine (5-Aza) markedly increased the proportion of CD4 + CD25 + regulatory T cells in peripheral blood mononuclear cells in culture and in diabetic animals. Adoptive transfer of immune cells from 5-Aza-treated animals showed beneficial effects on the host immune system, resulting in a significant improvement of DKD. Using genome-wide DNA methylation assays, we identified the differentially methylated cytosines in the promoter regions of mammalian target of rapamycin (mTOR) regulators in peripheral blood mononuclear cells of diabetic patients. Further, mRNA arrays confirmed the consistent induction of genes expressed in the mTOR pathway. Importantly, down-regulation of DNMT1 expression via RNA interference resulted in prominent cytosine demethylation of mTOR negative regulators and subsequent decrease of mTOR activity. Lastly, modulation of mTOR resulted in changes in the effect of 5-aza on diabetic immune cells. Thus, up-regulation of DNMT1 in diabetic immune cells induces aberrant cytosine methylation of the upstream regulators of mTOR, leading to pathogenic activation of the mTOR pathway and consequent inflammation in diabetic kidneys. Hence, this study highlights therapeutic potential of targeting epigenetic events in immune system for treating DKD., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Annually, 48,000 people die from pancreatic ductal adenocarcinoma (PDAC), ranking it the fourth among cancer-related deaths in the United States. Currently, anti-cancer drugs are not effective against PDAC, and only extends survival by 3 months. Aberrant DNA methylation has been shown to play an important role during carcinogenesis in PDAC, with approximately 80% of tumor overexpressing the DNA methyltransferase 1 (DNMT1) protein. In the present study, we used DNMTs as a screening platform to find a new DNMT inhibitor, n-butylidenephthalide (n-BP), which is identified from a Chinese herbal drug. n-BP could inhibit DNMT1 expression in both dose-dependent and time-dependent manner. It also displays an effect in suppressing growth of PDAC cells and inducing cell cycle arrest at G0/G1 phase leading apoptosis. Growth suppression can be restored by the overexpression of DNMT1 in PDAC cells. Furthermore, we found n-BP-mediated DNMT1 suppression influenced the protein stability rather than changing the RNA expression. Through microarray studies, we found that the patched domain contained 4 (PTCHD4) is the potential downstream gene of DNMT1. Following silencing of PTCHD4 expression by siRNA, n-BP decreased tumor growth inhibition. Finally, in vivo, two animal models were used to evaluate the efficacy and survival after n-BP treatment by interstitial control release polymer delivery. The results show that n-BP could effectively inhibit PDAC tumor volume growth and extend animal survival. In summary, n-BP may inhibit the growth of human PDAC cells though reducing DNMT1 and increasing the expression of PTCHD4 both in vitro and in vivo., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Ultraviolet (UV) radiation has been reported to influence epigenetic regulation by affecting the expression of genome regulators such as DNA methyltransferase 1 (DNMT1). DNMT1 is a "gene silencer," that is responsible for the maintenance of DNA methylation and contribution to de novo methylation. Implications of DNMT1's involvement in the expression of UV-induced proteins have been previously reported., Objective: To investigate for changes in DNA methylation-associated gene expressions by UV and to analyze the role of DNA methylation in the suppression of TIMP2 in UV-irradiated human skin., Methods: The expression of DNA methylation-associated proteins and TIMP2 were analyzed in UV-irradiated human skin in vivo and in human dermal fibroblasts in vitro. To investigate the relationship between DNMT1 and TIMP2, we assessed the effect of DNMT1 knockdown, inhibition and overexpression on TIMP2 levels in human dermal fibroblasts. Lastly, methylation-specific PCR was used to confirm increased DNA methylation in TIMP2 promoter in response to UV., Results: DNMT1 expression significantly increased whereas TIMP2 expression decreased in UV-irradiated human skin in vivo and in vitro. Downregulation of DNMT1 by knockdown or inhibition resulted in increased TIMP2 expression, whereas the overexpression of DNMT1 resulted in decreased TIMP2 expression. Lastly, methylation-specific PCR confirmed increased methylation on the CpG island residing in TIMP2 promoter in UV-irradiated human dermal fibroblasts., Conclusion: These findings suggest that UV-induced expression of DNMT1 may be responsible for mediating DNA hypermethylation in TIMP2, and thus, silencing its expression, in UV-exposed human skin., (Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Our perception of milk has changed from a "simple food" to a highly sophisticated maternal-neonatal nutrient and communication system orchestrating early programming of the infant. Milk miRNAs delivered by exosomes and milk fat globules derived from mammary gland epithelial cells play a key role in this process. Exosomes resist the harsh intestinal environment, are taken up by intestinal cells via endocytosis, and reach the systemic circulation of the milk recipient. The most abundant miRNA found in exosomes and milk fat globules of human and cow's milk, miRNA-148a, attenuates the expression of DNA methyltransferase 1, which is critically involved in epigenetic regulation. Another important miRNA of milk, miRNA-125b, targets p53, the guardian of the genome, and its diverse transcriptional network. The deficiency of exosomal miRNAs in infant formula and the persistent uptake of milk miRNAs after the nursing period via consumption of cow's milk are two epigenetic aberrations that may induce adverse long-term effects on human health., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

miR-140-5p is down-regulated in patients with pulmonary arterial hypertension (PAH) and experimental models of PAH, and inhibits hypoxia-mediated pulmonary artery smooth muscle cell (PASMC) proliferation in vitro. Delivery of synthetic miR-140-5p prevents and treats established, experimental PAH. DNA methyltransferase 1 (Dnmt1) is up-regulated in PAH associated human PASMCs (HPASMCs), which promotes the development of PAH by hypermethylation of CpG islands within the promoter for superoxide dismutase 2 (SOD2) and down-regulating SOD2 expression. We searched for miR-140-5p targets using TargetScan, PicTar and MiRanda tools, and found that Dnmt1 is a potential target of miR-140-5p. Based on these findings, we speculated that miR-140-5p might target Dnmt1 and regulate SOD2 expression to regulate hypoxia-mediated HPASMC proliferation, apoptosis and differentiation. We detected the expression of miR-140-5p, Dnmt1 and SOD2 by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays, respectively, and found down-regulation of miR-140-5p and SOD2 and up-regulation of Dnmt1 exist in PAH tissues and hypoxia-mediated HPASMCs. Cell proliferation, apoptosis and differentiation detection showed that miR-140-5p inhibits proliferation and promotes apoptosis and differentiation of HPASMCs in hypoxia, while the effect of Dnmt1 on hypoxia-mediated HPASMCs is reversed. Luciferase assay confirmed that miR-140-5p targets Dnmt1 directly. An inverse correlation is also found between miR-140-5p and Dnmt1 in HPASMCs. In addition, we further investigated whether miR-140-5p and Dnmt1 regulate HPASMC proliferation, apoptosis and differentiation by regulating SOD2 expression, and the results confirmed our speculation. Taken together, these results indicated that miR-140-5p at least partly targets Dnmt1 and regulates SOD2 expression to inhibit proliferation and promote apoptosis and differentiation of HPASMCs in hypoxia., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Adult neurogenesis persists throughout life in the dentate gyrus (DG) of the hippocampus, and its importance has been highlighted in hippocampus-dependent learning and memory. Adult neurogenesis consists of multiple processes: maintenance and neuronal differentiation of neural stem/precursor cells (NS/PCs), followed by survival and maturation of newborn neurons and their integration into existing neuronal circuitry. However, the mechanisms that govern these processes remain largely unclear. Here we show that DNA methyltransferase 1 (DNMT1), an enzyme responsible for the maintenance of DNA methylation, is highly expressed in proliferative cells in the adult DG and plays an important role in the survival of newly generated neurons. Deletion of Dnmt1 in adult NS/PCs (aNS/PCs) did not affect the proliferation and differentiation of aNS/PCs per se. However, it resulted in a decrease of newly generated mature neurons, probably due to gradual cell death after aNS/PCs differentiated into neurons in the hippocampus. Interestingly, loss of DNMT1 in post-mitotic neurons did not influence their survival. Taken together, these findings suggest that the presence of DNMT1 in aNS/PCs is crucial for the survival of newly generated neurons, but is dispensable once they accomplish neuronal differentiation in the adult hippocampus., (Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Conversion of hepatic stellate cells (HSCs) into hepatic myofibroblasts is a necessary event during the development of liver fibrosis. DNA methyltransferase 1 (DNMT1), which catalyzes DNA methylation and subsequently leads to the transcriptional repression of profibrotic genes, is selectively induced in myofibroblasts from diseased livers. Treatment of HSC with the DNA methylation inhibitor, 5-aza-2'-deoxycytidine (5-azadC), prevented TGF-β1-induced proliferation and alpha-smooth muscle actin (α-SMA) and collagen expression. 5-AzadC also rescued TGF-β1-induced suppression of Smad7 expression which occurs during HSC activation. Similarly, silencing the expression of the DNMT1 gene ameliorated the suppression of Smad7 expression by TGF-β1. In addition, DNMT1 inhibition, by 5-azadC or DNMT1 silencing, prevented the phosphorylation of Smad2 and Smad3. These studies suggest that epigenetic repression of Smad7 promotes the phosphorylation of Smad2 and Smad3 that may be an important molecular mechanism for perpetuated HSC activation and liver fibrosis., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: CD4+ T cells DNA hypomethylation is involved in the pathogenesis of systemic lupus erythematosus (SLE). Recent studies showed that ultraviolet B (UVB, 290-320 nm) might induce the exacerbation of SLE by decreasing the DNA methylation level. However, the role of DNA methyltransferase 1 (DNMT1) in the UVB-induced CD4+ T cells DNA hypomethylation remains unclear., Objective: To elucidate the role of DNMT1 in lupus CD4+ T cells global DNA hypomethylation enhanced by UVB., Methods: 35 SLE patients and 15 healthy controls were enrolled in the study. CD4+ T cells from SLE patients and healthy controls exposed to different dosages of UVB were analyzed. The global DNA methylation measurement, real-time PCR, Western blotting and DNMT1 catalytic activity detection were employed., Results: The level of global DNA methylation and DNMT1 mRNA expression in CD4+ T cells from SLE patients were significantly lower than those from the control group. DNA methylation was decreased after UVB exposure in a dosage-dependent manner in SLE patients, but not in the control group. DNMT1 mRNA and protein expression level were not affected by UVB exposure in both SLE patients and healthy controls. DNMT1 catalytic activity was significantly decreased in CD4+ T cells from SLE patients after UVB exposure in a dosage-dependent manner. DNMT1 catalytic activity was lower and more sensitive to UVB exposure in CD4+ T cells from active SLE patients that from stable ones., Conclusion: UVB enhanced DNA hypomethylation of CD4+ T cells in SLE via inhibiting DNMT1 catalytic activity in a dosage-dependent manner., (Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)