RNA traffic control of chromatin complexes

Abstract

It is widely accepted that the genome is regulated by histone modifications that induce epigenetic changes on the genome. However, it is still not understood how ubiquitously expressed chromatin modifying complexes are 'guided' to specific genomic sites to induce intricate patterns of epigenetic modifications. Previously believed to represent 'genome junk', it is now becoming increasingly clear that large non-coding RNAs associate with chromatin modifying complexes. Here we explore an intriguing hypothesis that large non-coding RNA molecules might represent a molecular trafficking system that modulates chromatin modifying complexes to establish specific epigenetic landscapes.

Figure 1

Model of large non-coding RNA function in cis versus trans (a) Cis model: large non-coding RNAs could serve as RNA based tethers to recruit either directly or indirectly epigenetic modifying complexes to the specific location of the RNA. (b) In trans, large non-coding RNAs could possibly target multiple sites of action.

Figure 2

Models how large non-coding RNAs could impart specificity to chromatin modifications (a) Cis model: at the site of RNA transcription, chromatin-modifying complexes could be recruited directly or indirectly and exert their function locally in cis. (b) Triple helix model: Formation of a RNA-DNA triplex could serve as a beacon to recruit directly or indirectly epigenetic modifying complexes to specific sites. (c) Infrastructure model: large non-coding RNAs could serve as an architectural scaffold that directly or indirectly links chromatin complexes to DNA binding proteins or transcription factors. (d) Allosteric model: RNA could bind directly or indirectly to chromatin remodeling proteins that change the shape of the protein or protein complex, activating/inactivating the complex and confer site specificity. (e) Looping model: RNA could serve as a scaffold to establish long range interactions via DNA looping and recruiting chromatin modifying complexes to distal sites of action in cis and or inter-chromosomal interactions (not shown).