Biology subjects

Marlin, M. N.

Publications and source records attributed to Marlin, M. N..

4 recordsLinked to original sources

bioRxiv2026

Defining cell type-specific diurnal gene expression in the mouse retina

The mammalian retina exhibits daily oscillations in gene expression that contribute to retinal physiology and visual function. However, the extent to which these temporal patterns differ among retinal cell types remains incompletely understood. We performed single-nucleus RNA sequencing in the mouse retina over the day and night, identifying rhythmic genes in the six major retinal cell types. Distinct diurnal gene expression patterns across photoreceptors, interneurons, retinal ganglion cells, and Muller glia correspond to their diverse functions across the light cycle. Even core circadian clock genes exhibited differences in paralog expression and rhythmicity across the retina. In contrast, dopamine signaling via the DRD4 receptor is highly rhythmic across most retinal cell types, suggesting dopamine signaling may be a key rhythmicity cue in the retina under diurnal conditions. This dataset highlights the complexity of daily transcriptional regulation in the retina and provides a resource to explore cell-type-specific diurnal rhythms.

neuroscience↗

bioRxiv2025

Broad epigenetic shifts in the aging Drosophila retina contribute to its altered rhythmic transcriptome.

Alterations in biological rhythms are a common feature of aging, and disruption of circadian rhythms can exacerbate age-associated pathologies. The retina is critical for detecting light for both vision and for transmitting time-of-day information to the brain, synchronizing rhythms throughout the body. Disruption of circadian rhythms by manipulating the molecular clock leads to premature retinal degeneration in flies and mice, and gene expression rhythms are disrupted in models of age-associated ocular disease. Despite this, it is unknown how or why the gene expression rhythms of the retina change with age. Here, we show that [~]70% of the Drosophila transcriptome is rhythmically expressed throughout the diurnal cycle, with [~]40% of genes showing altered rhythms with age. These transcriptome-wide changes in aging photoreceptors are accompanied by shifts in the rhythmic patterns of RNA Polymerase II (Pol II) occupancy, histone H3 lysine 4 (H3K4) methylation, and chromatin accessibility, without major changes in occupancy of the circadian clock transcription factors Clock (Clk) and Cycle (Cyc). Instead, aging decreases genome-wide levels of several different histone methyl marks including H3K4 methylation, whose relative levels across the day correlate with the phase of rhythmic gene expression. Moreover, individual knockdown of the three H3K4 methyltransferases in young photoreceptors results in massive disruptions to rhythmic gene expression that resemble those observed during aging. We conclude that there are broad epigenetic shifts in the aging retina, including decreased histone methylation, that contribute to changes in biological rhythms even in the presence of a robust molecular circadian clock.

molecular biology↗

bioRxiv2025

One-carbon metabolism enzyme Ahcy is a redox sensor that modulates gene expression to protect against light stress-induced retinal degeneration

One-carbon metabolism influences gene expression by providing methyl units for DNA, RNA, and histone methylation. Robust methylation requires rapid hydrolysis of the methylation by-product S-adenosylhomocysteine (SAH) by S-adenosylhomocysteinase (Ahcy). Here, we show Ahcy is a redox-sensitive enzyme that is inhibited by oxidation of a conserved cysteine, C195, in vitro and in vivo. Transient oxidation of Ahcy is neuroprotective in a Drosophila light stress model where it results in rapid gene expression changes and protects against retinal degeneration. Thus, redox sensing by the one-carbon metabolic enzyme Ahcy enables rapid changes in gene expression in response to changes in redox homeostasis.

biochemistry↗

bioRxiv2021

The Clock:cycle complex is a major transcriptional regulator of Drosophila photoreceptors that protects the eye from retinal degeneration and oxidative stress

The aging eye experiences physiological changes that include decreased visual function and increased risk of retinal degeneration. Although there are transcriptomic signatures in the aging retina that correlate with these physiological changes, the gene regulatory mechanisms that contribute to cellular homeostasis during aging remain to be determined. Here, we integrated ATAC-seq and RNA-seq data to identify 61 transcription factors that showed differential activity in aging Drosophila photoreceptors. These 61 age-regulated transcription factors include two circadian regulators, Clock and cycle, that showed sustained increases in activity during aging. When we disrupted Clock activity in adult photoreceptors, we observed changes in expression of 15 - 20% of genes including key components of the phototransduction machinery and many eye-specific transcription factors. Using ATAC-seq, we showed that loss of Clock activity leads to changes in activity of 31 transcription factors and causes a progressive decrease in global levels of chromatin accessibility in photoreceptors. Supporting a key role for Clock-dependent transcription in the eye, disruption of Clock activity in photoreceptors also induced light-dependent retinal degeneration and increased oxidative stress, independent of light exposure. Together, our data suggests that the circadian regulators Clock and cycle act as neuroprotective factors in the aging eye by directing gene regulatory networks that maintain expression of the phototransduction machinery and counteract oxidative stress.

genomics↗