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Aging is associated with enhanced chromatin compaction, global loss of H3 acetylation and local changes in transcription [ATAC-seq]

ABSTRACT: Advanced age is associated with specific alterations in organismic and cellular identity and behavior. To gain insights into age-associated rod photoreceptor function decline, we generated multi-omic datasets including 3D-genome topology, histone marks, chromatin accessibility, DNA methylation and transcriptome of rods from young- and aged-mice. We show global chromatin compaction during aging with regional alterations enriched at active chromatin. High-resolution microscopy leveraging the inverted nuclear architecture of mouse rods validates these findings. Chromatin dynamics broadly associate with epigenomic and transcriptional changes. Notably, a megabase-sized region presents multi-level alterations, with de novo transcription of a locus containing an open reading frame (ORF). This ORF encodes a functional histone acetyltransferase-inhibitor domain which transcription parallels H3 acetylation loss. Finally, we identify multiple highly significant local alterations of transcription at non-annotated regions and age-related macular degeneration genes. Our studies link age-related chromatin landscape changes and gene expression, potentially influencing rod function and vulnerability to diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE334819 | GEO | 2026/09/09

REPOSITORIES: GEO

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Project description:Tikidji-Hamburyan2018 - Rod phototransduction under strong illumination This model is described in the article: Rods progressively escape saturation to drive visual responses in daylight conditions. Tikidji-Hamburyan A, Reinhard K, Storchi R, Dietter J, Seitter H, Davis KE, Idrees S, Mutter M, Walmsley L, Bedford RA, Ueffing M, Ala-Laurila P, Brown TM, Lucas RJ, Münch TA. Nat Commun 2017 Nov; 8(1): 1813 Abstract: Rod and cone photoreceptors support vision across large light intensity ranges. Rods, active under dim illumination, are thought to saturate at higher (photopic) irradiances. The extent of rod saturation is not well defined; some studies report rod activity well into the photopic range. Using electrophysiological recordings from retina and dorsal lateral geniculate nucleus of cone-deficient and visually intact mice, we describe stimulus and physiological factors that influence photopic rod-driven responses. We find that rod contrast sensitivity is initially strongly reduced at high irradiances, but progressively recovers to allow responses to moderate contrast stimuli. Surprisingly, rods recover faster at higher light levels. A model of rod phototransduction suggests that phototransduction gain adjustments and bleaching adaptation underlie rod recovery. Consistently, exogenous chromophore reduces rod responses at bright background. Thus, bleaching adaptation renders mouse rods responsive to modest contrast at any irradiance. Paradoxically, raising irradiance across the photopic range increases the robustness of rod responses. This model is hosted on BioModels Database and identified by: MODEL1710030000. To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Aging is associated with enhanced chromatin compaction, global loss of H3 acetylation and local changes in transcription [ATAC-seq]

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