{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:00:50Z","timestamp":1782280850360,"version":"3.54.5"},"posted":{"date-parts":[[2025,6,17]]},"group-title":"Molecular Biology","reference-count":87,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["R01EY033734"],"award-info":[{"award-number":["R01EY033734"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  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 \u223c70% of the\n                  <jats:italic>Drosophila<\/jats:italic>\n                  transcriptome is rhythmically expressed throughout the diurnal cycle, with \u223c40% 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.\n                <\/jats:p>","DOI":"10.1101\/2025.06.17.660160","type":"posted-content","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:45:17Z","timestamp":1750207517000},"source":"Crossref","is-referenced-by-count":0,"title":["Broad epigenetic shifts in the aging\n                  <i>Drosophila<\/i>\n                  retina contribute to its altered rhythmic transcriptome"],"prefix":"10.64898","author":[{"given":"Sarah E.","family":"McGovern","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoya","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makayla N.","family":"Marlin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia A.","family":"Pruitt","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5933-9952","authenticated-orcid":false,"given":"Vikki M.","family":"Weake","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA"},{"name":"Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA"},{"name":"Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041204082353000_2025.06.17.660160v1.1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.178079.111"},{"key":"2026041204082353000_2025.06.17.660160v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20314-w"},{"key":"2026041204082353000_2025.06.17.660160v1.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1808137115"},{"key":"2026041204082353000_2025.06.17.660160v1.4","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"2026041204082353000_2025.06.17.660160v1.5","first-page":"01","article-title":"edgeR 4.0: powerful differential analysis of sequencing data with expanded functionality and improved support for small counts and larger datasets","volume":"2024","year":"2024","journal-title":"bioRxiv"},{"key":"2026041204082353000_2025.06.17.660160v1.6","doi-asserted-by":"crossref","unstructured":"Chen Y , Lun ATL & Smyth GK (2016) From reads to genes to pathways: Differential expression analysis of RNA-Seq experiments using Rsubread and the edgeR quasi-likelihood pipeline. 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