title: Epigenetic regulation of DNMT1 gene in mouse model of asthma disease.
abstract: Asthma is a complex genetic disease, which arises from the interaction of multiple genes and environmental stimuli. These influences are important to asthma pathogenesis. These can be mechanically explained by the Epigenetic phenomenon, which consists of the chromatin and its modifications, as well as a covalent modification of cytosines residing at the dinucleotide sequence CG in DNA by methylation. This reaction is catalyzed by a family of DNA methyltransferase enzyme (DNMTs). DNMT1 is one of them which maintained the methylation status during replication and also critical for the development, differentiation and regulation of Th1 and Th2 cells. Therefore we studied the DNMT1 mRNA expression profiling as well as CpG methylation status in promoter region. For these studies we developed asthma mouse model, and used Flow cytometer, qRT(2)-PCR, Methylation specific PCR, bisulfate conversion and BiQ analyzer. We found that DNMT1 expression level was low in all the tissues (lung, trachea and BALF cells) of asthmatic in comparison to normal mice. This was due to the methylation of regulatory sites of DNMT1 promoter region at cytosine residue. As the incidence of asthma is increasing globally and in world, this study assumes greater significance in designing and developing therapeutic means.
authors.affiliation: Immunobiology Division, CSIR-Indian Institute of Toxicology Research, M.G. Marg, Lucknow, 226001, India. mviitr@gmail.com
authors.forename: M
authors.initials: M
authors.lastname: Verma
authors.forename: B D
authors.initials: BD
authors.lastname: Chattopadhyay
authors.forename: B N
authors.initials: BN
authors.lastname: Paul
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001483:Base Sequence; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018899:CpG Islands; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007073:Immunoglobulin E; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619381:Dnmt1 protein, mouse