Cloning of DNA methyltransferase 1 (DNMT1)

Abstract

Cells of multicellular organisms are genetically homogenous but are heterogeneous in terms of morphology and functional specialization as a consequence of cell-specific expression of various sets of genes. During development, this cellular differentiation is established, maintained and changed in conjunction with cascades of transcription factors and epigenetic modulators such as DNA methylation, histone modifications, non-coding RNAs which work in tandem to co-ordinate the activity and regulation of the genome. DNA methylation is the principle epigenetic signal inducing genetic variation and plays a quintessential role in control of gene expression, cellular differentiation and development, preservation of chromosomal integrity, parental imprinting and X-chromosome inactivation. DNMT1, the maintenance methyltransferase is the main perpetuator of methylation, faithfully propagating existing methyl marks across successive cell divisions. Several intrinsic and extrinsic mechanisms in the mammalian cells regulate DNMT1 levels, their activity and stability including varied transcriptional activation of the respective genes, post-translational modifications of the enzyme, numerous interactions with other molecules involved in DNA methylation can affect catalytic activity, targeting and enzyme degradation at multiple levels . A comprehensive knowledge about DNMT1, its structural and functional organization, regulatory mechanisms and quantification of the various interactions is essential to elucidate its function at the molecular level and to understand the dynamics of DNA methylation at the cellular level. The present study was carried out to clone and characterize DNMT1. Further structure-function studies in this area will provide a comprehensive idea on DNMT1 function.