Long noncoding RNA-mediated i ntrachromosomal interactions promote imprinting at the Kcnq 1 locus.

Knqlotl is a long noncoding ribonucleic acid RNA; IncRNA) that participates in the regulation of genes within the Kcnql imprinting domain. Using a novel RNA-guided chromatin conformation capture method, we demonstrate that the 5' region of Kcnqlotl RNA orchestrates a long-range intrachromosomal loop between KvDMR1 and the Kcnql promoter that is required for maintenance of imprinting. PRC2 (polycomb repressive complex 2), which participates in the allelic repression of Kcnq 1, is also recruited by Kcnq Ioti RNA via EZH2. Targeted suppression of Kcnqlotl IncRNA prevents the creation of this long-range intrachromosomal loop and causes loss of Kcnq 1 imprinting. These observations delineate a novel mechanism by which an IncRNA directly builds an intrachromosomal interaction complex to establish allele-specific transcriptional gene silencing over a large chromosomal domain. [ABSTRACT FROM AUTHOR]