title: Factors modifying transcriptional regulation of signaling genes have putative role in tumor development and progression in humans.
abstract: Genes involved in signaling are highly regulated at the level of transcription. Several factors have been known to play role in transcriptional modification of genes. Among these DNA sequence variations present in the regulatory region and aberrant methylation of CpG Iceland in promoter region are the most important factors modifying transcriptional regulation of genes. DNA sequence variation interferes with assembling of regulatory protein TF (transcription factor) on the cis elements TFBS (transcription factor binding site). Presence of variations in regulatory region may alter the level of gene product via interaction of TF to TFBS (transcriptional modification). Promoter hypermethylation causes gene silencing and responsible for transcriptional dysregulation of gene. JAK-1, STAT-3, IL-6, MAPK and AR genes participate in signaling pathway and are tightly regulated. Overexpression of IL-6 and activated STAT3 may contribute to the development of prostate cancer and possibly other human cancers. Indeed, constitutively activated STAT3 have been found in a growing number of human tumors. In the present work, we have predicted 34 regulatory polymorphisms that lies in TFBS of 5 (JAK-1, STAT-3, IL-6, MAPK and AR) signaling genes and compare the methylation of CpG Iceland in promoter region of above motioned genes. On the basis of these predictions, it has been hypothesized that transcriptional modification of gene resulting from the DNA sequence variations in regulatory region or promoter hypermethylation increases the susceptibility to diseases such as cancer by alteration in the level of signaling genes product. Presence of DNA sequence variations may also influence the response to a particular drug.
authors.affiliation: Department of Biotechnology, FET, RBS College, Agra, India. tabish.qidwai@gmail.com
authors.forename: M Tabish
authors.initials: MT
authors.lastname: Qidwai
authors.forename: Farrukh
authors.initials: F
authors.lastname: Jamal
authors.forename: Dharmendrapal
authors.initials: D
authors.lastname: Singh
authors.forename: Ratnesh K
authors.initials: RK
authors.lastname: Sharma
mesh_terms: D019175:DNA Methylation; D018450:Disease Progression; D005786:Gene Expression Regulation; D006801:Humans; D008962:Models, Theoretical; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000235:genetics*; D014158:Transcription, Genetic