Kcnq1ot1 Antisense Noncoding RNA Mediates Lineage-Specific Transcriptional Silencing through Chromatin-Level Regulation
Kcnq1ot1 Antisense Noncoding RNA Mediates Lineage-Specific Transcriptional Silencing through Chromatin-Level Regulation
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DOI：
10.1016/j.molcel.2008.08.022
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发表时间：
2008-10-24
期刊：
影响因子：
16
通讯作者：
Kanduri, Chandrasekhar
中科院分区：
文献类型：
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作者：
Pandey, Radha Raman;Mondal, Tanmoy;Kanduri, Chandrasekhar
近期的研究表明长链反义非编码RNA参与染色体区域的表观遗传调控。在此我们发现Kcnq1ot1是一种由RNA聚合酶II编码的、长91kb且具有一定稳定性的核转录本，并且其稳定性对于Kcnq1区域内基因的双向沉默至关重要。Kcnq1ot1以一种谱系特异性的方式与染色质以及H3K9和H3K27特异性组蛋白甲基转移酶G9a和PRC2复合物相互作用。这种相互作用与胎盘中Kcnq1区域内富含H3K9me3和H3K27me3的染色质延伸区域的存在相关，而胎儿肝脏则既没有这些染色质相互作用也没有异染色质结构。此外，与肝脏相比，Kcnq1区域在胎盘中更常与核仁区室接触。综上所述，我们的数据描述了一种机制，即Kcnq1ot1通过招募染色质重塑复合物建立谱系特异性转录沉默模式，并通过将相关区域靶向核仁周区室从而在后续细胞分裂过程中维持这些模式。
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.