Global chromatin relabeling accompanies spatial inversion of chromatin in rod photoreceptors

The nuclear architecture of rod photoreceptor cells in nocturnal mammals is unlike that of other animal cells. Murine rod cells have an “inverted” chromatin organization with euchromatin at the nuclear periphery and heterochromatin packed in the center of the nucleus. In conventional nuclear architecture, euchromatin is mostly in the interior, and heterochromatin is largely at the nuclear periphery. We demonstrate that inverted nuclear architecture is achieved through global relabeling of the rod cell epigenome. During rod cell maturation, H3K9me2-labeled nuclear peripheral heterochromatin is relabeled with H3K9me3 and repositioned to the nuclear center, while transcriptionally active euchromatin is labeled with H3K9me2 and positioned at the nuclear periphery. Global chromatin relabeling is correlated with spatial rearrangement, suggesting a critical role for histone modifications, specifically H3K9 methylation, in nuclear architecture. These results reveal a dramatic example of genome-wide epigenetic relabeling of chromatin that accompanies altered nuclear architecture in a postnatal, postmitotic cell.