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Biology subjects

Sethuraman, S.

Publications and source records attributed to Sethuraman, S..

2 recordsLinked to original sources

Invivo and systematic analysis of random multigenic deletions associated with human diseases during epithelial morphogenesis using Drosophila

Random loss of multigenic loci on chromosomes, a crucial drive for evolution, occurs frequently in all living organisms. Analysis of such chromosomal disruption and understanding the consequences of their impact on the growth and development of multicellular organisms is challenging. In this report, we have addressed this issue using invivo mosaic analysis of deficiency lines in Drosophila. Genes on fly deficiency lines were compared with human orthologs for their implications in disease development during cytoskeletal processes and epithelial morphogenesis. The cytoskeletal phenotypes from the fly has been utilized to predict the function of human orthologs. In addition, as these Drosophila deficiency lines are equivalent to human microdeletions, based on the clonal behaviour and phenotypes generated, a systematic analysis has been carried out to establish the critical loci that correspond to Microdeletion Syndromes and Mendelian Disorders in humans. Further we have drawn the synteny that exists between these chromosomes and have identified critical region corresponding to defects. A few potential candidates that might have an implication in epithelial morphogenesis are also identified.

genetics↗

DNA methylation directs nucleosome positioning in RNA-mediated transcriptional silencing

Repressive chromatin modifications are instrumental in regulation of gene expression and transposon silencing. In Arabidopsis thaliana, transcriptional silencing is performed by the RNA-directed DNA methylation (RdDM) pathway. In this process, two specialized RNA polymerases, Pol IV and Pol V, produce non-coding RNAs, which recruit several RNA-binding proteins and lead to the establishment of repressive chromatin marks. An important feature of chromatin is nucleosome positioning, which has also been implicated in RdDM. We show that RdDM affects nucleosomes via the SWI/SNF chromatin remodeling complex. This leads to the establishment of nucleosomes on methylated regions, which counteracts the general depletion of DNA methylation on nucleosomal regions. Nucleosome placement by RdDM has no detectable effects on the pattern of DNA methylation. Instead, DNA methylation by RdDM and other pathways affects nucleosome positioning. We propose a model where DNA methylation serves as one of the determinants of nucleosome positioning.

plant biology↗