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BACKGROUND:Periodontitis is an inflammatory and destructive disease with plaque biofilm as the main pathogenic material,which occurs in the gingiva,periodontal ligament,alveolar bone and cementum.The antigen of bacterial complex and its secreted toxin and enzyme directly lead to the destruction of periodontal tissue and trigger the host's immune response,causing indirect damage to the body tissue.Silence information regulatory factors(Sirtuins,SIRTs)play an important role in anti-aging,anti-oxidative stress,regulating inflammation,and mediating autophagy,and are closely related to the occurrence and development of periodontitis. OBJECTIVE:To review the research status of Sirtuins in periodontitis. METHODS:The first author used the computer to search the relevant research regarding the role of Sirtuins in periodontitis in PubMed,Web of Scene,CNKI and WanFang databases.The key words were"Sirtuins,Sirtuin1-7,periodontitis"in English and Chinese.After literature screening,57 articles were included for review and analysis. RESULTS AND CONCLUSION:SIRT1,SIRT2,SIRT3,and SIRT6 participate in regulating the occurrence and development of periodontitis.Inhibition of SIRT1 expression may be the target of periodontitis treatment,while overexpression of SIRT1 can inhibit periodontitis and protect periodontal tissue.The activator of SIRT1 can reduce the inflammation of periodontal tissue and improve the systemic pathological changes caused by periodontitis.SIRT2 is involved in nicotinamide phosphoribosyltransferase-mediated periodontal inflammation and plays a role in the treatment and prognosis of periodontal diseases.SIRT3 can improve age-related periodontal disease.Gastrodin promotes the osteogenic differentiation of periodontal ligament stem cells through the up-regulation of SIRT3.The activator of SIRT3 reduces the damage of periodontitis to periodontal and renal tissues by regulating the level of autophagy in the cells.SIRT6 can inhibit the inflammatory reaction of periodontal tissue and inhibit the differentiation and mineralization of cementoblasts.SIRT6 is beneficial to the prognosis of periapical periodontitis.The relationship between SIRT4,SIRT5,SIRT7 and periodontitis is rarely reported.
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@#Histone acetylation and methylation can affect chromatin conformation and regulate a variety of biological activities. Abnormal histone acetylation and methylation modifications are related to the occurrence and development of a variety of oral diseases. Histone acetylation and methylation increase or decrease in an orderly manner to regulate the development of teeth. Fluoride ions can destroy the balance between histone acetylation and methylation, which may be related to the occurrence of dental fluorosis. In addition, histone acetylation and methylation are involved in the regulation of oral inflammatory diseases. In the inflammatory microenvironment, the expression of histone acetyltransferase GCN5 decreases, and the expression of Dickkopf 1 (DKK1) decreases, activating the Wnt/β-catenin pathway and ultimately inhibiting the osteogenic differentiation of periodontal ligament stem cells. Enhancer of zeste homolog 2 (EZH2) and H3K27me3 levels were decreased in inflamed dental pulp tissues and cells. EZH2 inhibition inhibited the expression of interleukin (IL)-1b, IL-6 and IL-8 in human dental pulp cells under inflammatory stimulation. Histone acetylation/methylation modifications can interact with multiple signaling pathways to promote the occurrence and development of oral tumors and are related to the high invasiveness of salivary gland tumors. Small molecule drugs targeting histone acetylation and methylation-related enzymes can regulate the level of histone methylation/acetylation and have shown potential in the treatment of oral and maxillofacial diseases. For example, the histone deacetylase inhibitor vorinostat can inhibit the secretion of inflammation-related cytokines; it also promotes the maturation of odontoblasts and the formation of dentin-related matrix, demonstrating its potential in pulp preservation. Understanding the role of histone acetylation/methylation modifications in the occurrence and development of oral diseases will help promote research on epigenetic modifications in oral diseases and provide new perspectives for disease diagnosis and treatment.
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Epilepsy is a complex neurological disease and its pathogenesis has not yet been clear. More and more evidence shows that epilepsy is closely related to epigenetic mechanisms such as histone deacetylation. Histone deacetylase inhibitors, a kind of epilepsy targeting drug potentially, are involved in the protection of neurogenesis and the regulation of a variety of neural signal cascade reactions. This article reviews the research progress of histone deacetylation in the pathogenesis of epilepsy and application prospect of histone deacetylase inhibitors in treating epilepsy.
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Objective To explore the mechanism of hepatitis B virus X protein down-regulating DKK4 and its effect on the proliferation, migration of HCC cell lines. Methods HCC cell lines HepG2 and SMMC7721 cells were infected with adenovirus encoding hepatitis B virus X protein (Ad-HBx), and GFP adenovirus (Ad-GFP) was designed as a control group. We used deacetylase inhibitor (TSA) to treat HCC cell lines and transfected HCC cell lines with small interfering RNA-histone deacetylase 1 (si-HDAC1) and lentivirus overexpressing DKK4. Western blot was used to detect the expression of DKK4, HDAC1 and SIRT1. The proliferation and migration ability of HCC lines were assessed using MTT, crystal violet experiment and Transwell experiment. Results DKK4 expression level was significantly downregulated after Ad-HBx infection (P < 0.05), and its expression level was recovered after TSA treatment (P < 0.05). After silencing HDAC1 with small interfering RNA, the expression of DKK4 could be restored (P < 0.05), the proliferation and migration of HDAC1-silencing or/and DKK4-overexpressing cells decreased (P < 0.05). Conclusion Hepatitis B virus X protein inhibits the expression of DKK4 protein by up-regulating HDAC1 and SIRT1. Silencing HDAC1 and over expressing DKK4 protein could inhibit the proliferation and migration of HCC cell lines infected with Ad-HBx.
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Alzheimer’s disease (AD) is a neurodegenerative disease, β-amyloid (Aβ) deposition and Tau protein hyperphosphorylation are the main pathological features. Silent mating-type information regulation 2 homolog 1 (SIRT1) can deacetylate various types of histones and non-histones, and play an important role in the pathogenesis of AD. Recent studies found that exercise can activate SIRT1 to delay the progression of AD. The mechanisms may be as follows: inhibit the activity of β-secretase and increase the activity of α-secretase to reduce the production of Aβ; reduce the accumulation of hyperphosphorylated Tau protein; interact with PGC-1α to promote mitochondrial biogenesis; up-regulate PINK1/ Parkin signaling pathway to improve mitochondrial autophagy; and deacetylate NF-κB to inhibit neuroinflammation. In addition, the protein levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in hippocampus are increased, and ApoE4 gene is inhibited to enhance synaptic plasticity. This article summarizes the role and mechanisms of exercise in improving AD by regulating SIRT1, and provides new ideas for the prevention and treatment of AD.
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TANK-binding kinase 1 (TBK1), a core kinase of antiviral pathways, activates the production of interferons (IFNs). It has been reported that deacetylation activates TBK1; however, the precise mechanism still remains to be uncovered. We show here that during the early stage of viral infection, the acetylation of TBK1 was increased, and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1. HDAC3 directly deacetylated TBK1 at Lys241 and Lys692, which resulted in the activation of TBK1. Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively. Using knockout cell lines and transgenic mice, we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs. Furthermore, activated TBK1 phosphorylated HDAC3, which promoted the deacetylation activity of HDAC3 and formed a feedback loop. In this study, we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-translational modulations involved in the interaction between TBK1 and HDAC3.
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Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke, but how to control the overactive neuroinflammation is still a long-standing challenge. Here, we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia, which were abolished by silencing SIRT6. RNA-seq screening identified the forkhead box C1 (
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Objective:To evaluate the role of nicotinamide adenine dinucleotide (NAD + )-mediated deacetylation activity of silent information regulator 1 (SIRT1) in endotoxin-induced acute lung injury (ALI) in mice. Methods:Twenty-five SPF clean-grade healthy male C57BL/6 mice including 10 wild-type (WT) and 15 NMNAT1 conditional-knockout (KO) mice, aged 6-8 weeks, weighing 20-25 g, were selected.The WT mice were divided into 2 groups ( n=5 each) using a random number table method: control group (group WT+ C) and ALI group (group WT+ ALI). The KO mice were divided into 3 groups ( n=5 each) using a random number table method: control group (group KO+ C), ALI group (group KO+ ALI) and ALI plus NAD + precursor substances nicotinamide mononucleotide (NMN) group (KO+ LPS+ NMN group). ALI was produced with lipopolysaccharide (LPS) 15 mg/kg injected intravenously.NMN 500 mg/kg was intraperitoneally injected at 1 h before injection of LPS in KO+ ALI+ NMN group, while the equal volume of normal saline was given instead in control group.Blood samples were collected from the abdominal aorta at 12 h after LPS or normal saline injection for blood gas analysis, and the animals were then sacrificed and the lung tissues were removed for microscopic examination of pathologic changes which were scored and for determination of wet/dry weight ratio (W/D ratio), and interleukin-6 (IL-6), IL-1β and tumor necrosis factor-alpha (TNF-α) contents (by enzyme-linked immunosorbent assay)and content of NAD + (using a spectrophotometer) and levels of SIRT1, acetylated nuclear factor kappaB (Ac-NF-κB), acetylated p53 (Ac-p53), acetylated FoxO1 (Ac-FoxO1) and acetylated PGC1α (Ac-PGC1α) (by Western blot). Results:Compared with group C, pH value and PaO 2 were significantly decreased, the PaCO 2, W/D ratio, lung injury score, contents of IL-6, IL-1β, TNF-α and NAD + were increased, expression of SIRT1 was up-regulated, and expression of Ac-NF-κB, Ac-p53, Ac-FoxO1 and Ac-PGC1α was down-regulated in group ALI ( P<0.05). Compared with group WT+ ALI, pH value and PaO 2 were significantly decreased, the PaCO 2, W/D ratio, lung injury score, contents of IL-6, IL-1β and TNF-α were increased, NAD + content was decreased, expression of SIRT1 was down-regulated, and expression of Ac-NF-κB, Ac-p53, Ac-FoxO1 and Ac-PGC1α was up-regulated in group KO+ ALI ( P<0.05). Compared with group KO+ ALI, pH value and PaO 2 were significantly increased, the PaCO 2, W/D ratio, lung injury score, contents of IL-6, IL-1β and TNF-α were decreased, NAD + content was increased, expression of SIRT1 was up-regulated, and expression of Ac-NF-κB, Ac-p53, Ac-FoxO1 and Ac-PGC1α was down-regulated in group KO+ ALI+ NMN ( P<0.05). Conclusion:The enhanced NAD + -mediated deacetylation activity of SIRT1 is involved in the endogenous protective mechanism in mice with endotoxin-induced ALI.
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Sirtuins belongs to the class III family of histone deacetylases (HDAC), which is a mammalian homolog of the yeast silencing information regulator Sir2. Silent information regulator factor 2-related enzyme 1 (SIRT1) is the most well studied family member of Sirtuins. Distributed mainly in the nucleus and cytoplasm, SIRT1 is involved in various intracellular biological processes, including DNA damage repair, gene transcription, energy metabolism, stress and apoptosis through its NAD
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Osteoporosis is a bone disease characterized by low bone mass and deteriorated bone microstructure, which could be related to the disorders of energy metabolism and bone senescence. Silent mating-type information regulator 2 homolog 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that regulates cell senescence, energy metabolism and bone remodeling. SIRT1 could be activated not only by adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), c-Jun N-terminal kinase 1 (JNK1) and casein kinase 2 (CK2), but also by small-molecular drugs such as resveratrol. All these kinases and drugs can affect bone metabolism. Recent findings indicate that SIRT1 signaling pathway plays a direct role in bone metabolism, but the underlying mechanism remains unclear. This paper reviews the structure and function of SIRT1, and the role of SIRT1 in bone metabolism, and discusses the potential of SIRT1 signaling pathway as a new therapeutic target in osteoporosis.
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As a member of the Sirtuins family in mammals, SIRT7 locates in nucleus and is a highly specific H3K18Ac (acetylated lysine 18 of histone H3) deacetylase. Recent studies showed that SIRT7 could participate in the ribosomal RNA transcription, cell metabolism, cell stress and DNA damage repair through various signaling pathways. In addition, SIRT7 is also closely related with aging, heart disease and fatty liver. In particular, SIRT7 plays important roles in the regulation of initiation and development of various tumors, such as liver cancer, gastric cancer, breast cancer, bladder cancer, colorectal cancer, and head/neck squamous cell carcinoma. This review describes the cellular and molecular functions of SIRT7, and systematically summarizes recent progress of SIRT7 in human disease.
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Animals , Humans , Histones , Lysine , Neoplasms , Signal Transduction , Sirtuins , MetabolismABSTRACT
Histone acetylation is one of the most important reactions of post-translational modification of histones, which plays an important role in the regulation of epigenetic processes. Histone deacetylase 2 as a member of type I histone deacetylases,involved in the catalytic regulation of histone and a variety of non-histone deacetylation,regulates a variety of life processes. This paper summarizes the basic structure of histone deacetylase 2 and the role of histone deacetylase 2 in various diseases,and provides a theoretical basis for conducting related studies.
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Objective To investigate the effect and molecular mechanism of botulinum neurotoxin serotype A (BoNT/A) heavy chain on neuron regeneration. Methods Cell culture, rats, immunofluorescence, SDS-PAGE and western blot, etc. were adopted in this study to explore the alterations of histone-3 acetylation (acetyl-H3 ) by local treatment of BoNT/A heavy chain to spinal cord injury (SCI) in rats (in vivo) or by adding it into cell culture (in vitro). Meanwhile, the relevance of acetyl-H3 to neurite out-growth based on SCI and cell culture with BoNT/A heavy chain application was approached as well. Results The application of BoNT/A heavy chain to cultured Neuro-2a cells increased the level of H3 acetylation. The increase of H3 acetylation was paralleled with the growth of neuritogenesis. Also, the neuronal treatment of BoNT/A heavy chain to SCI promoted the re-growth of neuronal processes surrounding the lesions. The growth of neuronal processes was positively correlated to the level of H3 acetylation. During the periods of BoNT/A heavy chain treatment in vivo or in vitro, the increase of H3 acetylation showed two peaks. Conclusions BoNT/A heavy chain increased the H3 acetylation, which might be one of its neuritogenic mechanisms.
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Cardiovascular disease is a serious disease harmful to human health with high morbidity and high mortality.SIRT6 plays an important role in cardiovascular diseases such as atherosclerosis,myocardial infarction and ischemia/reperfusion injury,pathological cardiac hypertrophy and heart failure,as an important member of the histone deacetylase family.In this paper,the role of SIRT6 in cardiovascular diseases is reviewed,and the development of SIRT6 as a target agonist and inhibitor is summarized.
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Microglia play a pivotal role in clearance of Aβ by degrading them in lysosomes, countering amyloid plaque pathogenesis in Alzheimer's disease (AD). Recent evidence suggests that lysosomal dysfunction leads to insufficient elimination of toxic protein aggregates. We tested whether enhancing lysosomal function with transcription factor EB (TFEB), an essential regulator modulating lysosomal pathways, would promote Aβ clearance in microglia. Here we show that microglial expression of TFEB facilitates fibrillar Aβ (fAβ) degradation and reduces deposited amyloid plaques, which are further enhanced by deacetylation of TFEB. Using mass spectrometry analysis, we firstly confirmed acetylation as a previously unreported modification of TFEB and found that SIRT1 directly interacted with and deacetylated TFEB at lysine residue 116. Subsequently, SIRT1 overexpression enhanced lysosomal function and fAβ degradation by upregulating transcriptional levels of TFEB downstream targets, which could be inhibited when TFEB was knocked down. Furthermore, overexpression of deacetylated TFEB at K116R mutant in microglia accelerated intracellular fAβ degradation by stimulating lysosomal biogenesis and greatly reduced the deposited amyloid plaques in the brain slices of APP/PS1 transgenic mice. Our findings reveal that deacetylation of TFEB could regulate lysosomal biogenesis and fAβ degradation, making microglial activation of TFEB a possible strategy for attenuating amyloid plaque deposition in AD.
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Animals , Humans , Mice , Alzheimer Disease , Metabolism , Pathology , Amyloid beta-Peptides , Metabolism , Amyloid beta-Protein Precursor , Genetics , Metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors , Chemistry , Genetics , Metabolism , Brain , Metabolism , Cells, Cultured , Chloride Channels , Genetics , Metabolism , Disease Models, Animal , HEK293 Cells , Lysosomes , Genetics , Metabolism , Mice, Transgenic , Microglia , Cell Biology , Metabolism , Mutagenesis, Site-Directed , Peptides , Chemistry , Protein Binding , RNA Interference , Sirtuin 1 , Genetics , MetabolismABSTRACT
Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may influence asthma pathogenesis; however, its roles in regulating specific molecular transcription mechanisms remain unclear. We aimed to investigate the effect of 1,25(OH)2D3 on the expression and enzyme activity of histone deacetylase 2 (HDAC2) and its synergistic effects with dexamethasone (Dx) in the inhibition of inflammatory cytokine secretion in a rat asthma model. Healthy Wistar rats were randomly divided into 6 groups: control, asthma, 1,25(OH)2D3 pretreatment, 1,25(OH)2D3 treatment, Dx treatment, and Dx and 1,25(OH)2D3 treatment. Pulmonary inflammation was induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA). Inflammatory cells and cytokines in the bronchoalveolar lavage (BAL) fluid and histological changes in lung tissue were examined. Nuclear factor kappa B (NF-κB) p65 and HDAC2 expression levels were assessed with Western blot analyses and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Enzyme activity measurements and immunohistochemical detection of HDAC2 were also performed. Our data demonstrated that 1,25(OH)2D3 reduced the airway inflammatory response and the level of inflammatory cytokines in BAL. Although NF-κB p65 expression was attenuated in the pretreatment and treatment groups, the expression and enzyme activity of HDAC2 were increased. In addition, 1,25(OH)2D3 and Dx had synergistic effects on the suppression of total cell infusion, cytokine release, and NF-κB p65 expression, and they also increased HDAC2 expression and activity in OVA/OVA rats. Collectively, our results indicated that 1,25(OH)2D3 might be useful as a novel HDAC2 activator in the treatment of asthma.
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Animals , Male , Asthma/drug therapy , Calcitriol/pharmacology , /drug effects , NF-kappa B/drug effects , Vitamins/pharmacology , Asthma/chemically induced , Blotting, Western , Bronchoalveolar Lavage Fluid/chemistry , Cell Count , Calcitriol/therapeutic use , Cytokines/analysis , Cytokines/drug effects , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation, Enzymologic/drug effects , /metabolism , Immunohistochemistry , Lung/chemistry , Lung/drug effects , NF-kappa B/analysis , Ovalbumin , Rats, Wistar , Real-Time Polymerase Chain Reaction , Reproducibility of Results , Treatment Outcome , Vitamins/therapeutic useABSTRACT
Background: Asthma is common chronic disease worldwide. Methylxanthines has been used in the treatment of asthma. The study was undertaken to compare two Methylxanthines theophylline and doxofylline at doses recommended and commonly used in clinical practice in Mild Bronchial Asthma Patients. Methods: Study was conducted in patients of Mild Bronchial Asthma in TB and chest disease department of a medical college hospital. It was randomized, prospective and open label. A total of 107 patients were divided in two group .Group I was administered 400 mg theophylline SR once daily and group II was administered doxofylline 400 mg twice a day orally. Spirometric variables symptom score, and adverse effects were recorded on day 0, 7 and 21 of therapy. Data were compared and analysed using SPSS version 16. Results: Results of the study showed that there was significant improvement in spirometric variables and clinical symptom score compared to pretreatment values after medication in both groups on 7th and 21st days of treatment. But there was no statistically significant difference between improvement in theophylline and doxofylline groups with respect to spirometric variables and symptom score. There was no significant difference in two groups with respect to side effects (p>0.05). Conclusions: It is concluded in Patients of mild Bronchial Asthma Theophylline and doxofylline improve the spirometric and clinical symptoms and doxofylline has no advantage over theophylline in terms of either efficacy or safety on the doses commonly used in current clinical practice.
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Objective To examine the effect of Scriptaid,a histone deacetylase inhibitor and a kind of anti-cancer drug,on development of mouse somatic cell nuclear transfer (SCNT) embryos in vitro and explore a new strategy to improve the efficiency of SCNT. Methods SCNT was carried out by pizeo-activated micromanipulator in C57/BL6 mouse,from which the oocytes were chsoen as recipients and the cumulus cells as donors.The rcconstructcd embryos were randomly divided into 5 groups and activated in calcium-free activators with 0 mmol/L (negative control group),and 50,100,250 and 500 mmol/L Scriptaid for 6 h, respectively; and then, they were transferred into KSOM medium with corresponding concentrations of Scriptaid for 4 h.The cloned embryos were finally cultured in KSOM medium for 96 h.The development (form rate) of cloned embryos and the count of blastocysts cells were recorded. Results No significant differences on the activated rate of the reconstructed embryos and the 2-cell cleavage rate were noted between each 2 groups (P＞).05).However,the form rate (24.2％) and cell numbers (56.27±2.43) of blastocysts in 250 mmol/L Scriptaid activation group were significantlyhigher as compared with those in the negative control group, and 50, 100 and 500 mmol/L Scriptaid activation groups (form rates:5.3％,6.5％,9.4％ and 6.9％; cell numbers:44.67±1.53,50.25±1.26,52.33±2.50 and 50.75±1.50,respectively,P＜0.05). Conclusion The early development potential of mouse SCNT embryos in vitro can be dramatically improved by 250mmol/L Scriptaid.
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BACKGROUND: It has generally been proven that histone acetylation and deacetylation are involved in the malignant transformation. To date, however, this has rarely been studied in cases of malignant lymphoma. METHODS: We studied nine cases of reactive lymphoid hyperplasia, 78 cases of diffuse large B-cell lymphoma (DLBCL), 13 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), and 13 cases of extranodal NK/T-cell lymphoma, nasal type (NKTCL). Thus, we attempted to elucidate the associations of the degree of the expression of histone acetyltransferase 1 (HAT1), histone deacetylase (HDAC) 1, HDAC2, and HDAC3 with the clinical behaviors of above malignant lymphomas using the immunohistochemistry and a western blot analysis. RESULTS: The degree of the expression of HAT1 was higher in cases of DLBCL, PTCL-NOS or NKTCL as compared with reactive lymphoid hyperplasia (p0.05). CONCLUSIONS: HAT1, HDAC1, and HDAC2 play a critical role in the development of malignant lymphomas. Both HAT1 and HDAC1 might be indicators for a poor prognosis in cases of DLBCL as cooperating factors.
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Acetylation , B-Lymphocytes , Blotting, Western , Histone Acetyltransferases , Histone Deacetylase Inhibitors , Histone Deacetylases , Histones , Immunohistochemistry , Lymphoma , Lymphoma, B-Cell , Lymphoma, T-Cell, Peripheral , Prognosis , PseudolymphomaABSTRACT
A potential strategy to combat obesity and its associated complications involves modifying gene expression in adipose cells to reduce lipid accumulation. The nuclear receptor Peroxisome Proliferator-activated receptor gamma (PPARγ) is the master regulator of adipose cell differentiation and its functional activation is currently used as a therapeutic approach for Diabetes Mellitus type 2. However, total activation of PPARγ induces undesirable secondary effects that might be set with a partial activation. A group of proteins that produce histone demethylation has been shown to modify the transcriptional activity of nuclear receptors. Here we describe the repressive action of the jumonji domain containing 2C/lysine demethylase 4 C (JMJD2C/KDM4C) on PPARγ transcriptional activation. JMJD2C significantly reduced the rosiglitazone stimulated PPARγ activation. This effect was mainly observed in experiments performed using the Tudor domains that may interact with histone deacetylase class 1 (HDAC) and this interaction probably reduces the mediated activation of PPARγ. Trichostatin A, a HDAC inhibitor, reduces the repressive effect of JMJD2C. When JMJD2C was over-expressed in 3T3-L1 cells, a reduction of differentiation was observed with the Tudor domain. In summary, we herein describe JMJD2C-mediated reduction of PPARgamma transcriptional activation as well as preadipocyte differentiation. This novel action of JMJD2C might have an important role in new therapeutic approaches to treat obesity and its complications.