Aging is associated with a decline in visual function and increased prevalence of ocular disease, correlating with changes in the transcriptome and epigenome of cells in the eye. Here, we sought to identify the transcriptional mechanisms that are necessary to maintain photoreceptor viability and function during aging. To do this, we performed a targeted photoreceptor-specific RNAi screen in to identify transcriptional regulators whose knockdown results in premature, age-dependent retinal degeneration.
View Article and Find Full Text PDFEmbryonic expression of DNMT3B is critical for establishing de novo DNA methylation. This study uncovers the mechanism through which the promoter-associated long non-coding RNA (lncRNA) Dnmt3bas controls the induction and alternative splicing of Dnmt3b during embryonic stem cell (ESC) differentiation. Dnmt3bas recruits the PRC2 (polycomb repressive complex 2) at cis-regulatory elements of the Dnmt3b gene expressed at a basal level.
View Article and Find Full Text PDFStudies in multiple organisms have shown that aging is accompanied by several molecular phenotypes that include dysregulation of chromatin. Since chromatin regulates DNA-based processes such as transcription, alterations in chromatin modifications could impact the transcriptome and function of aging cells. In flies, as in mammals, the aging eye undergoes changes in gene expression that correlate with declining visual function and increased risk of retinal degeneration.
View Article and Find Full Text PDFIn mammals, DNA methyltransferases DNMT1 and DNMT3's (A, B and L) deposit and maintain DNA methylation in dividing and nondividing cells. Although these enzymes have an unremarkable DNA sequence specificity (CpG), their regional specificity is regulated by interactions with various protein factors, chromatin modifiers, and post-translational modifications of histones. Changes in the DNMT expression or interacting partners affect DNA methylation patterns.
View Article and Find Full Text PDFThe orange carotenoid protein (OCP) mediates nonphotochemical quenching (NPQ) mechanisms in cyanobacteria. A bound ketocarotenoid serves as a sensor of midvisible light intensity and as a quencher of phycocyanobilin excitons in the phycobilisome. The photochemical mechanism that triggers conversion of the protein from a resting, orange state (OCP) to an active, red state (OCP) after optical preparation of the S state of the carotenoid remains an open question.
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