Stable C0T-1 Repeat RNA Is Abundant and Is Associated with Euchromatic Interphase Chromosomes

Recent studies recognize a vast diversity of noncoding RNAs with largely unknown functions, but few have examined interspersed repeat sequences, which constitute almost half our genome. RNA hybridization in situ using C0T-1 (highly repeated) DNA probes detects surprisingly abundant euchromatin-associated RNA comprised predominantly of repeat sequences (C0T-1 RNA), including LINE-1. C0T-1-hybridizing RNA strictly localizes to the interphase chromosome territory in cis and remains stably associated with the chromosome territory following prolonged transcriptional inhibition. The C0T-1 RNA territory resists mechanical disruption and fractionates with the nonchromatin scaffold but can be experimentally released. Loss of repeat-rich, stable nuclear RNAs from euchromatin corresponds to aberrant chromatin distribution and condensation. C0T-1 RNA has several properties similar to XIST chromosomal RNA but is excluded from chromatin condensed by XIST. These findings impact two “black boxes” of genome science: the poorly understood diversity of noncoding RNA and the unexplained abundance of repetitive elements. [Display omitted] •Abundant euchromatin-associated chromosomal RNA is predominantly C0T-1 repeat RNA•Stable C0T-1 RNA remains localized to the chromosome long after transcription arrest•C0T-1 RNA fractionates with nonchromatin scaffold and disperses upon its disruption•Repeat-rich chromosomal RNA is silenced by XIST RNA and may promote open euchromatin Abundant amounts of repeat-containing RNA are found to be stably associated with euchromatin and may contribute to maintenance of chromatin structure.