Long Noncoding RNA-mediated Intrachromosomal Interactions Promote Imprinting at the Kcnq1 Locus

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2014 Jan 8

PMID 24395636

Citations 75

Authors

He Zhang

Michael J Zeitz

Hong Wang

Beibei Niu

Shengfang Ge

Wei Li

Jiuwei Cui

Guanjun Wang

Guanxiang Qian

Michael J Higgins

Xianqun Fan

Andrew R Hoffman

Ji-Fan Hu

Affiliations

Soon will be listed here.

Abstract

Kcnq1ot1 is a long noncoding ribonucleic acid (RNA; lncRNA) that participates in the regulation of genes within the Kcnq1 imprinting domain. Using a novel RNA-guided chromatin conformation capture method, we demonstrate that the 5' region of Kcnq1ot1 RNA orchestrates a long-range intrachromosomal loop between KvDMR1 and the Kcnq1 promoter that is required for maintenance of imprinting. PRC2 (polycomb repressive complex 2), which participates in the allelic repression of Kcnq1, is also recruited by Kcnq1ot1 RNA via EZH2. Targeted suppression of Kcnq1ot1 lncRNA prevents the creation of this long-range intrachromosomal loop and causes loss of Kcnq1 imprinting. These observations delineate a novel mechanism by which an lncRNA directly builds an intrachromosomal interaction complex to establish allele-specific transcriptional gene silencing over a large chromosomal domain.

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