Promoter targeted small RNAs induce long-term transcriptional gene silencing in human cells.
Promoter targeted small RNAs induce long-term transcriptional gene silencing in human cells.
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DOI：
10.1093/nar/gkp127
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发表时间：
2009-05
影响因子：
14.9
通讯作者：
Morris KV
中科院分区：
文献类型：
--
作者：
Hawkins PG;Santoso S;Adams C;Anest V;Morris KV
靶向人类细胞基因启动子的小RNA可以通过将沉默状态表观遗传修饰引导到靶基因座来介导转录基因沉默（TGS）。这一过程的许多机制细节仍然不清楚，以这种方式稳定调节基因表达的能力尚未得到探索。在这里，我们描述的机制，建立和维护的长期转录沉默的人泛素C基因（UbC）。用小RNA持续靶向UbC启动子至少3天导致长期沉默，这与靶向基因座处组蛋白甲基化的早期增加和DNA甲基化的后期增加相关。UbC的转录沉默需要启动子相关RNA的存在。TGS的建立和维持需要不同的蛋白质因子。Argonaute 1（Ago 1）、DNA甲基转移酶3a（DNMT 3a）和组蛋白去乙酰化酶1（HDAC 1）是启动沉默所必需的，DNA甲基转移酶1（DNMT 1）是维持沉默所必需的。总之，这里提供的数据突出了非编码RNA相互作用的细胞途径，以表观遗传学方式调节人类细胞中的基因表达。
Small RNAs targeted to gene promoters in human cells can mediate transcriptional gene silencing (TGS) by directing silent state epigenetic modifications to targeted loci. Many mechanistic details of this process remain poorly defined, and the ability to stably modulate gene expression in this manner has not been explored. Here we describe the mechanisms of establishment and maintenance of long-term transcriptional silencing of the human ubiquitin C gene (UbC). Sustained targeting of the UbC promoter with a small RNA for a minimum of 3 days resulted in long-term silencing which correlated with an early increase in histone methylation and a later increase in DNA methylation at the targeted locus. Transcriptional silencing of UbC required the presence of a promoter-associated RNA. The establishment and maintenance of the TGS were shown to require distinct protein factors. Argonaute 1 (Ago1), DNA methyltransferase 3a (DNMT3a) and histone deacetylase 1 (HDAC1) were required for the initiation of silencing, and DNA methyltransferase 1 (DNMT1) was necessary for maintenance. Taken together the data presented here highlight the cellular pathway with which noncoding RNAs interact to epigenetically regulate gene expression in human cells.
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DOI：
10.1073/pnas.0808830105
发表时间：
2008-10-21
影响因子：
11.1
作者：
Kim, Daniel H.;Saetrom, Pal;Rossi, John J.
通讯作者：
Rossi, John J.
影响因子：
5.3
作者：
Liang, GG;Chan, MF;Jones, PA
通讯作者：
Jones, PA
影响因子：
16.8
作者：
Janowski, Bethany A.;Huffman, Kenneth E.;Corey, David R.
通讯作者：
Corey, David R.
影响因子：
56.9
作者：
Ogawa, Yuya;Sun, Bryan K.;Lee, Jeannie T.
通讯作者：
Lee, Jeannie T.
影响因子：
4.3
作者：
Gonzalez, Susana;Pisano, David G.;Serrano, Manuel
通讯作者：
Serrano, Manuel