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DNA methyltransferase 1(DNMT1) induced the expression of suppressors of cytokine signaling3 (Socs3) in a mouse model of asthma

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Abstract

DNMT1 is the most important methyltransferase enzyme, involved in the regulation of gene expression and appropriate histone modification. It interact with proliferating cell nuclear antigen (PCNA), SNF2 family member ATP-dependent chromatin remodeling enzyme, cyclin dependent kinases inhibitor, E2F1 transcription factor and HDACs to form a repressor complex known as HDAC complexes. The interaction of DNMT1 with numerous protein suppressors of promoters suggests that the enzyme is a crucial element of the transcription suppression complex. Since the mechanism behind over expression of Socs3 in Asthma is unclear, we study the Epigenetic mode of overexpression of Socs3 in terms of methylation/acetylation/inactivation of HDACs/activation of HATs enzymes in a mouse model of asthma. The results show that low expression of DNMT1 might indirectly induce the expression of Socs3 and HAT, and inhibit the expression of HDACs family. Furthermore knockdown of DNMT1 by siRNA induced expression of Socs3 while knock down of Socs3 by siRNA has no effect on DNMT1 expression. Our result suggests that the over expression of Socs3 is due to the inhibition of HDACs complex and hyperacetylation of histones molecule along with down regulation of DNMT1 gene. In depth study on DNMT1 might be useful for the development of therapeutic drug against asthma/allergic diseases.

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Acknowledgments

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. C. Kesavachandran, Dr. Dhirendra Singh, Dr Mahadeo Kumar, for encouragement and inspiration. I am obliged to technical staff of this institution who helped us to peruse this work. We are thankful to Dr S.L Nagale Immunobiology division who has helped us a lot. I am especially thankful to Dr. Amit Sharma for manuscript preparation. This work was financially supported by the Indian Council of Medical Research, New Delhi.

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Authors and Affiliations

  1. Immunobiology Division, CSIR-Indian Institute of Toxicology Research, Lucknow, 226001, India

    M. Verma

  2. Department of Physics, Jadavpur University, Kolkata, India

    B. D. Chattopadhyay

  3. Animal Facility CSIR-Indian Institute of Toxicology Research, Lucknow, India

    S. Kumar

  4. Regional Research Institute of Unani Medicine, Bhadrak, Odisha, India

    K. Kumar

  5. Pathology Division, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Rae Bareli Rd, Lucknow, 226014, Uttar Pradesh, India

    D. Verma

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  1. M. Verma
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Correspondence to M. Verma.

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Verma, M., Chattopadhyay, B.D., Kumar, S. et al. DNA methyltransferase 1(DNMT1) induced the expression of suppressors of cytokine signaling3 (Socs3) in a mouse model of asthma. Mol Biol Rep 41, 4413–4424 (2014). https://doi.org/10.1007/s11033-014-3312-5

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