Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes

TLDR

Long noncoding RNAs are largely uncharacterized, but the lincRNA HOTAIR, transcribed from the mouse HOXC locus, recruits Polycomb Repressive Complex 2 to target genes to repress transcription. The study shows that HOTAIR simultaneously binds PRC2 and the LSD1‑CoREST/REST complex, acting as a scaffold that coordinates their recruitment to target genes. Tsai et al.

Abstract

A Lot of HOTAIR The roles of several classes of small (<50 nucleotides) noncoding RNAs are beginning to be defined in molecular detail, whereas the function of most of the long (∼200+ nucleotides), intergenic noncoding (linc)RNAs found in most eukaryotic genomes remains something of a mystery. The HOTAIR lincRNA, which is transcribed from the mouse HOXC locus, binds to the Polycomb Repressive Complex 2 (PRC2) and recruits it to HOXD and other genes, where its histone methylase activity acts to repress gene transcription. Tsai et al. (p. 689 , published online 8 July) now show that HOTAIR also binds to a histone demethylase enzyme, LSD1, part of the CoREST/REST repressor complex. LSD1 acts to remove transcription-activating histone marks, reinforcing the repressive activity of the PRC2 complex. HOTAIR thus functions as a platform for the coordinated binding of PRC2 and LSD1-containing complexes to genes, as revealed in a genome-wide analysis of PRC1/CoREST/REST co-regulated genes.