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

Abstract

SUMMARY Recent studies recognize a vast diversity of non-coding RNAs with largely unknown functions, but few have examined interspersed repeat sequences, which constitute almost half our genome. RNA hybridization in situ using CoT-1 (highly repeated) DNA probes detects surprisingly abundant euchromatin-associated RNA comprised predominantly of repeat sequences (“CoT-1 RNA”), including LINE-1. CoT-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 CoT-1 RNA territory resists mechanical disruption and fractionates with the non-chromatin scaffold, but can be experimentally released. Loss of repeat-rich, stable nuclear RNAs from euchromatin corresponds to aberrant chromatin distribution and condensation. CoT-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 non-coding RNA and the unexplained abundance of repetitive elements.

Comprehensive characterization of neutrophil genome topology

“…LINE-1 elements are scattered across the genome and enriched in the B compartment and reposition at a global scale during neutrophil differentiation. A role for a subset of LINE-1 elements in structuring the genome has been proposed previously for X-chromosome inactivation and chromosome contraction (Chow et al 2010;Corbel et al 2013;Hall et al 2014). Along the same line, we suggest that, during neutrophil differentiation, LINE-1 elements promote chromosome contraction by sequestering large portions of the neutrophil genome to the lamina.…”

LINEs in mice: features, families, and potential roles in early development

“…Evidence in support of this hypothesis comes from experiments in which L1 transcripts have been shown to act as scaffolds that bind euchromatic DNA. After their removal, condensation of chromatin occurs, suggesting the importance of L1 transcripts in keeping a more open chromatin configuration (Hall et al 2014). An open chromatin state is one of the hallmarks of early embryogenesis and has been associated to totipotency (Boskovic et al 2014), which would explain the reason for keeping high transcription of L1 elements after fertilization and their subsequent silencing.…”

The increasing diversity of functions attributed to the SAFB family of RNA-/DNA-binding proteins

“…Although a possible role for the SAFB proteins in X chromosome inactivation has not been investigated, SAFA is known to be essential for chromosomal localisation of XIST, the SAP domain as well as the RGG/RG domain being involved [24]. With the increasing realisation that non-coding RNAs (such as long interspersed nuclear elements, LINEs) are likely to be important components of chromatin structure [56], recent studies with the SAP domain of SAFA are of particular interest and may be relevant to understanding SAFB function. For example, the dominant negative C280 mutant of SAFA, which lacks the N-terminal sequence including the SAP domain, was shown to cause the release of LINE RNA and consequent chromatin condensation.…”