RAKESH K MISHRA
Articles written in Journal of Biosciences
Volume 43 Issue 4 September 2018 pp 621-633 Article
Nuclear Matrix (NuMat) is the structural and functional framework of the nucleus. It has been shown that attachment ofchromatin to NuMat brings significant regulation of the transcriptional activity of particular genes; however, key componentsof NuMat involved in this process remain elusive. We have identified Lid (Little imaginal discs) as one of thecomponents of NuMat. It belongs to the TrxG group of proteins involved in activation of important developmental genes.However, unlike other activator proteins of TrxG, Lid is a Jumonji protein involved in H3K4me3 demethylation. Here, wereport the association of Lid and its various domains with NuMat which implicates its structural role in chromatinorganization and epigenetic basis of cellular memory. We have found that both N and C terminal regions of this protein arecapable of associating with NuMat. We have further mapped the association of individual domains and found that, PHD,ARID and JmjC domains can associate with NuMat individually. Moreover, deletion of N-terminal PHD finger does notalter Lid’s NuMat association implying that although it is sufficient, yet, it is not necessary for Lid’s structural role inNuMat. Based on our findings, we hypothesize that C terminal region of Lid which contains PHD fingers might beresponsible for its NuMat association via protein–DNA interactions. However, for the N terminal region harboring both aPHD and an ARID finger, Lid anchors to the NuMat via both protein-protein and protein-DNA interactions. The associationof JmjC domain with NuMat is the first report of the association of a demethylase domain with NuMat suggesting that Lid,a demethylase, being part of NuMat might be involved in regulating the chromatin dynamics via its NuMat association.
Volume 45 All articles Published: 20 January 2020 Article ID 0012 Article
The epigenetic memory is an essential aspect of multicellular organisms to maintain several cell types and their geneexpression pattern. This complex process uses a number of protein factors and specific DNA elements within thedevelopmental cues to achieve this. The protein factors involved in the process are the Polycomb group (PcG)members, and, accordingly, the DNA sequences that interact with these proteins are called Polycomb ResponseElements (PREs). Since the PcG proteins are highly conserved among higher eukaryotes, including insects, andfunction at thousands of sites in the genomes, it is expected that PREs may also be present across the genome.However,the studies on PREs in insect species, other thanDrosophila, is currently lacking.We took a bioinformatics approach todevelop an inclusive PRE prediction tool, ‘PRE Mapper’, to address this need. By applying this tool on the Drosophilamelanogaster genome, we predicted more than 20,000 PREs.When compared with the available PRE prediction methods, thistool shows far better performance by correctly identifying the in vivo binding sites of PcG proteins, identified bygenome-scale ChIP experiments. Further analysis of the predicted PREs shows their cohabitation with chromatindomain boundary elements at several places in the Drosophila genome, possibly defining a composite epigeneticmodule.We analysed 10 insect genomes in this context and find several conserved features in PREs across the insectspecies with some variations in their occurrence frequency. These analyses leading to the identification of PREin insectgenomes contribute to our understanding of epigenetic mechanisms in these organisms.
Volume 45 All articles Published: 10 February 2020 Article ID 0038 Article
GAGA associated factor (GAF) is a sequence-specific DNA binding transcription factor that is evolutionarilyconserved from flies to humans. Emerging evidence shows a context-dependent function of vertebrate GAF(vGAF, a.k.a. ThPOK) in multiple processes like gene activation, repression, and enhancer-blocking. Wehypothesize that context-dependent interaction of vGAF with a diverse set of proteins forms the basis for themultifunctional nature of vGAF. To this end, we deciphered the protein–protein interactome of vGAF andshow that vGAF interacts with chromatin remodelers, RNA metabolic machinery, transcriptional activators/repressors, and components of DNA repair machinery. We further validated the biological significance of ourprotein–protein interaction data with functional studies and established a novel role of vGAF in DNA repairand cell-survival after UV-induced DNA damage. One of the major risk factors for skin cutaneous melanoma isprolonged exposure of UV and subsequent DNA damage. vGAF is highly expressed in normal skin tissue.Interestingly, our analysis of high-throughput RNA-sequencing data shows that vGAF is heavily downregulatedacross all major stages of skin cutaneous melanoma suggesting its potential as a diagnostic biomarker.Taken together, our study provides a plausible explanation for the diverse gene regulatory functions of vGAFand unravels its novel role in DNA repair.
Volume 45, 2020
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