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

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).