Kcnq1ot1 Antisense Noncoding RNA Mediates Lineage-Specific Transcriptional Silencing through Chromatin-Level Regulation

被引：991

作者：

Pandey, Radha Raman ^{[1
]}

Mondal, Tanmoy ^{[1
]}

Mohammad, Faizaan ^{[1
]}

Enroth, Stefan ^{[2
]}

Redrup, Lisa ^{[3
]}

Komorowski, Jan ^{[2
]}

Nagano, Takashi ^{[4
]}

Mancini-DiNardo, Debora ^{[5
]}

Kanduri, Chandrasekhar ^{[1
]}

机构：

[1] Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, S-75185 Uppsala, Sweden

[2] Uppsala Univ, Linnaeus Ctr Bioinformat, BMC, SE-75124 Uppsala, Sweden

[3] Babraham Inst, Lab Dev Genet & Imprinting, Cambridge CB22 3AT, England

[4] Babraham Inst, Lab Chromatin & Gene Express, Cambridge CB22 3AT, England

[5] Myriad Genet, Salt Lake City, UT 84108 USA

来源：

MOLECULAR CELL | 2008年 / 32卷 / 02期

基金：

瑞典研究理事会; 英国医学研究理事会;

关键词：

D O I：

10.1016/j.molcel.2008.08.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Recent investigations have implicated long antisense noncoding RNAs in the epigenetic regulation of chromosomal domains. Here we show that Kcnq1ot1 is an RNA polymerase II-encoded, 91 kb-long, moderately stable nuclear transcript and that its stability is important for bidirectional silencing of genes in the Kcnq1 domain. Kcnq1ot1 interacts with chromatin and with the H3K9- and H3K27-specific histone methyltransferases G9a and the PRC2 complex in a lineage-specific manner. This interaction correlates with the presence of extended regions of chromatin enriched with H3K9me3 and H3K27me3 in the Kcnq1 domain in placenta, whereas fetal liver lacks both chromatin interactions and heterochromatin structures. In addition, the Kcnq1 domain is more often found in contact with the nucleolar compartment in placenta than in liver. Taken together, our data describe a mechanism whereby Kcnq1ot1 establishes lineage-specific transcriptional silencing patterns through recruitment of chromatin remodeling complexes and maintenance of these patterns through subsequent cell divisions occurs via targeting the associated regions to the perinucleolar compartment.

引用

页码：232 / 246

页数：15

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