Biology subjects

Nishana, M.

Publications and source records attributed to Nishana, M..

3 recordsLinked to original sources

bioRxiv2023

AMLdb: A comprehensive multi-omics platform to understand the pathogenesis and discover biomarkers for acute myeloid leukemia

Acute myeloid leukemia (AML) is one of the leading leukemic malignancies in adults. The heterogeneity of the disease makes the diagnosis and treatment extremely difficult. Despite the significant developments and the rapid advancements in finding new medication targets, the treatment for AML remains a challenge. With the advent of next-generation sequencing (NGS) technologies, exploration at the molecular level for the identification of biomarkers and drug targets has been the main focus for the researchers to come up with novel therapies for better prognosis and survival outcomes of AML patients. However, the massive amounts of data generated from the NGS platforms demands the necessity to create a comprehensive platform on AML to save the time invested in mining literature. To facilitate this, we developed AMLdb, an interactive multi-omics platform that allows users to query, visualize, retrieve and analyze AML-related multi-omics data. It provides a diverse collection of data resourced from various repositories allowing for a more comprehensive analysis. AMLdb contains 86 datasets for gene expression profiles, 15 datasets for methylation profiles, CRISPR-Cas9 knockout screens of 26 AML cell lines, sensitivity of 26 AML cell lines to 288 drugs, mutations in 41 unique genes in 23 AML cell lines and information on 27 experimentally validated biomarkers. The data provided can be used for deriving conclusions on potential targets for therapies, sensitivity of these targets towards the drugs, patient classification, prediction of treatment strategies and outcomes, chances of relapse etc. In this study, we have reported five genes i.e., CBFB, ENO1, IMPDH2, SEPHS2 and MYH9 identified via our analysis using AMLdb as potential targets. Amongst this, CBFB, IMPDH2, SEPHS2 and MYH9 have been previously validated as targets by experimental studies which is in par with our results. However, ENO1 is a novel target identified using AMLdb which needs further investigation. We anticipates that, AMLdb can be a valuable resource to aid the research community accelerate the development of effective therapies for AML. AMLdb is freely accessible at https://project.iith.ac.in/cgntlab/amldb/ without any restrictions.

genomics↗

bioRxiv2019

Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation

BackgroundUbiquitously expressed CTCF is involved in numerous cellular functions, such as organizing chromatin into TAD structures. In contrast, its paralog, CTCFL is normally only present in testis. However, it is also aberrantly expressed in many cancers. While it is known that shared and unique zinc finger sequences in CTCF and CTCFL enable CTCFL to bind competitively to a subset of CTCF binding sites as well as its own unique locations, the impact of CTCFL on chromosome organization and gene expression has not been comprehensively analyzed in the context of CTCF function. Using an inducible complementation system, we analyze the impact of expressing CTCFL and CTCF-CTCFL chimeric proteins in the presence or absence of endogenous CTCF to clarify the relative and combined contribution of CTCF and CTCFL to chromosome organization and transcription. ResultsWe demonstrate that the N terminus of CTCF interacts with cohesin which explains the requirement for convergent CTCF binding sites in loop formation. By analyzing CTCF and CTCFL binding in tandem we identify phenotypically distinct sites with respect to motifs, targeting to promoter/intronic intergenic regions and chromatin folding. Finally, we reveal that the N, C and zinc finger terminal domains play unique roles in targeting each paralog to distinct binding sites, to regulate transcription, chromatin looping and insulation. ConclusionThis study clarifies the unique and combined contribution of CTCF and CTCFL to chromosome organization and transcription, with direct implications for understanding how their co-expression deregulates transcription in cancer.

genomics↗

bioRxiv2019

RNA interactions with CTCF are essential for its proper function

The function of the CCCTC-binding factor (CTCF) in the organization of the genome has become an important area of investigation, but the mechanisms of how CTCF dynamically contributes to genome organization is not clear. We previously discovered that CTCF binds to large numbers of endogenous RNAs; promoting its oligomerization. Here we found that inhibition of transcription or interfering with CTCF ability to bind RNA through mutations of two of its 11 zinc fingers that are not involved with CTCF binding to its cognate site in vitro, zinc finger-1 (ZF1) or -10 (ZF10), disrupt CTCF association to chromatin. These mutations alter gene expression profiles as CTCF mutants lose their ability to promote local insulation. Our results highlight the importance of RNA as a structural component of the genome, in part by affecting the association of CTCF with chromatin and likely its interaction with other factors. O_LITranscriptional inhibition disrupts CTCF binding to chromatin C_LIO_LIRNA-binding regions (RBR) in CTCF are found within ZF1 and ZF10 C_LIO_LILocal insulation is markedly decreased in ZF1{triangleup} and ZF10{triangleup} mutant rescues C_LIO_LIGene expression and chromatin organization are disrupted by RBR mutants C_LI

molecular biology↗