Long noncoding RNA-mediated intrachromosomal interactions promote imprinting at the Kcnq1 locus

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 intrachromosom...

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Bibliographic Details
Published in:The Journal of cell biology 2014-01, Vol.204 (1), p.61-75
Main Authors: Zhang, He, Zeitz, Michael J, Wang, Hong, Niu, Beibei, Ge, Shengfang, Li, Wei, Cui, Jiuwei, Wang, Guanjun, Qian, Guanxiang, Higgins, Michael J, Fan, Xianqun, Hoffman, Andrew R, Hu, Ji-Fan
Format: Article
Language:English
Subjects:
Alleles
Animals
Cell Line
Cellular biology
Chromatin - genetics
Cyclin-Dependent Kinase Inhibitor p57 - genetics
DNA - genetics
DNA Methylation
Female
Gene Silencing
Genes
Genetics
Genomic Imprinting - genetics
KCNQ1 Potassium Channel - genetics
Male
Mice
Mice, Inbred C57BL
Polycomb Repressive Complex 2 - genetics
Promoter Regions, Genetic
Proteins
Ribonucleic acid
RNA
RNA, Long Noncoding - genetics
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Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201304152