Epigenetic regulation of DNMT1 gene in mouse model of asthma disease
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, qRT2-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.
KeywordsAsthma Epigenetic DNMT1 CpG methylation
We thank Dr. K.C. Gupta, Director, Indian Institute of Toxicology Research for support and encouragement. We would like to express our gratitude to Dr. K.P. Singh, Dr. Dhirendra Singh, Dr. Mahadev Kumar, for encouragement and inspiration. I am obliged to technical staff of this institution who helped us to peruse this work. I thankful to Dr. S.L. Nagale Immunobiology division helped us lot. This work was financially supported by the Indian Council of Medical Research, New Delhi.
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