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Singh V.,National Institute of Pathology ICMR | Singh L.C.,National Institute of Pathology ICMR | Vasudevan M.,Bionivid Technology Pvt. Ltd. | Chattopadhyay I.,Central University of Tamil Nadu | And 8 more authors.
OMICS A Journal of Integrative Biology

Esophageal cancer is a major global health burden with a strong host-environment interaction component and epigenomics underpinnings that remain to be elucidated further. Certain populations such as the Northeast Indians suffer at a disproportionately higher rate from this devastating disease. Promoter methylation is correlated with transcriptional silencing of various genes in esophageal cancer. Very few studies on genome-wide methylation for esophageal cancer exist and yet, no one has carried out an integromics analysis of methylation and gene expression. In the present study, genome-wide methylation was measured in samples collected from the Northeast Indian population by Infinium 450k array, and integration of the methylation data was performed. To prepare a network of genes displaying enriched pathways, together with the list of genes exhibiting promoter hypermethylation or hypomethylation with inversely correlated expression, we performed an integrome analysis. We identified 23 Integrome network enriched genes with relevance to tumor progression and associated with the processes involved in metastasis such as cell adhesion, integrin signaling, cytoskeleton, and extracellular matrix organizations. These included four genes (PTK2, RND1, RND3, and UBL3) with promoter hypermethylation and downregulation, and 19 genes (SEMG2, CD97, CTNND2, CADM3, OMD, NEFM, FBN2, CTNNB1, DLX6, UGT2B4, CCDC80, PZP, SERPINA4, TNFSF13B, NPC1, COL1A1, TAC3, BMP8A, and IL22RA2) with promoter hypomethylation and upregulation. A Methylation Efficiency Index was further calculated for these genes; the top five gene with the highest index were COL1A1, TAC3, SERPINA4, TNFSF13B, and IL22RA2. In conclusion, we recommend that the circulatory proteins IL22RA2, TNFSF13B, SERPINA4, and TAC3 in serum of patients and disease-free healthy controls can be examined in the future as putative noninvasive biomarkers. © Copyright 2015, Mary Ann Liebert, Inc. Source

Banerjee A.,Saha Institute of Nuclear Physics | Sanyal S.,Saha Institute of Nuclear Physics | Kulkarni K.K.,Bionivid Technology Pvt. Ltd. | Jana K.,Bose Institute of India | And 3 more authors.
FEBS Open Bio

Mithramycin (MTR) is a clinically approved DNA-binding antitumor antibiotic currently in Phase 2 clinical trials at National Institutes of Health for treatment of osteosarcoma. In view of the resurgence in the studies of this generic antibiotic as a human medicine, we have examined the binding properties of MTR with the integral component of chromatin - histone proteins - as a part of our broad objective to classify DNA-binding molecules in terms of their ability to bind chromosomal DNA alone (single binding mode) or both histones and chromosomal DNA (dual binding mode). The present report shows that besides DNA, MTR also binds to core histones present in chromatin and thus possesses the property of dual binding in the chromatin context. In contrast to the MTR-DNA interaction, association of MTR with histones does not require obligatory presence of bivalent metal ion like Mg2+. As a consequence of its ability to interact with core histones, MTR inhibits histone H3 acetylation at lysine 18, an important signature of active chromatin, in vitro and ex vivo. Reanalysis of microarray data of Ewing sarcoma cell lines shows that upon MTR treatment there is a significant down regulation of genes, possibly implicating a repression of H3K18Ac-enriched genes apart from DNA-binding transcription factors. Association of MTR with core histones and its ability to alter post-translational modification of histone H3 clearly indicates an additional mode of action of this anticancer drug that could be implicated in novel therapeutic strategies. © 2014 The Authors. Source

Banerjee A.,Saha Institute of Nuclear Physics | Sanyal S.,Saha Institute of Nuclear Physics | Majumder P.,Saha Institute of Nuclear Physics | Chakraborty P.,Bionivid Technology Pvt. Ltd. | And 3 more authors.
Biochemical and Biophysical Research Communications

Abstract Recognition of core histone components of chromatin along with chromosomal DNA by a class of small molecule modulators is worth examining to evaluate their intracellular mode of action. A plant alkaloid ellipticine (ELP) which is a putative anticancer agent has so far been reported to function via DNA intercalation, association with topoisomerase II and binding to telomere region. However, its effect upon the potential intracellular target, chromatin is hitherto unreported. Here we have characterized the biomolecular recognition between ELP and different hierarchical levels of chromatin. The significant result is that in addition to DNA, it binds to core histone(s) and can be categorized as a 'dual binder'. As a sequel to binding with histone(s) and core octamer, it alters post-translational histone acetylation marks. We have further demonstrated that it has the potential to modulate gene expression thereby regulating several key biological processes such as nuclear organization, transcription, translation and histone modifications. © 2015 Elsevier Inc. Source

Kakumani P.K.,International Center for Genetic Engineering and Biotechnology | Shukla R.,Bionivid Technology Pvt. Ltd. | Todur V.N.,Bionivid Technology Pvt. Ltd. | Malhotra P.,International Center for Genetic Engineering and Biotechnology | And 3 more authors.
Biology Direct

Spodoptera is an important polyphagous agricultural insect pest in the tropical world. The genomic details are limited to understand the pest biology at molecular level. In the present study, we sequenced and assembled the transcriptome from Sf21 cells into a non redundant set of 24,038 contigs of ~ 47.38 Mb in size. A total of 26,390 unigenes were identified from the assembled transcripts and their annotation revealed the prevalent protein domains in Sf21 cells. The present study would provide a resource for gene discovery and development of functional molecular markers to understand the biology of S. frugiperda. Reviewers: This article was reviewed by Dr. Thiago Motta Venancio and Prof. Michael Gray. © 2015 Kakumani et al. Source

Kulkarni K.K.,Bionivid Technology Pvt. Ltd. | Bankar K.G.,Bionivid Technology Pvt. Ltd. | Shukla R.N.,Bionivid Technology Pvt. Ltd. | Das C.,Saha Institute of Nuclear Physics | And 3 more authors.
Genomics Data

The role of Mithramycin as an anticancer drug has been well studied. Sarcoma is a type of cancer arising from cells of mesenchymal origin. Though incidence of sarcoma is not of significant percentage, it becomes vital to understand the role of Mithramycin in controlling tumor progression of sarcoma. In this article, we have analyzed the global gene expression profile changes induced by Mithramycin in two different sarcoma lines from whole genome gene expression profiling microarray data. We have found that the primary mode of action of Mithramycin is by global repression of key cellular processes and gene families like phosphoproteins, kinases, alternative splicing, regulation of transcription, DNA binding, regulation of histone acetylation, negative regulation of gene expression, chromosome organization or chromatin assembly and cytoskeleton. © 2014. Source

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