Non-coding RNA derived from the region adjacent to the human HO-1 E2 enhancer selectively regulates HO-1 gene induction by modulating Pol II binding.
Non-coding RNA derived from the region adjacent to the human HO-1 E2 enhancer selectively regulates HO-1 gene induction by modulating Pol II binding.
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DOI：
10.1093/nar/gku1169
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发表时间：
2014-12-16
影响因子：
14.9
通讯作者：
Itoh K
中科院分区：
文献类型：
--
作者：
Maruyama A;Mimura J;Itoh K
增强子RNA（enhancerRNA，eRNA）是由基因增强子区域转录的长链非编码RNA，近年来的研究揭示了其在转录调控中的作用。然而，目前还不清楚eRNA是否参与了人类血红素加氧酶-1基因（HO-1）诱导的调控。在这里，我们报告了多种富含核的eRNA从与两个人类HO-1增强子（即远端E2和近端E1增强子）相邻的区域转录，其中一些eRNA是由氧化应激引起的试剂马来酸二乙酯诱导的（DEM）。我们证明，在HeLa细胞中，DEM以NRF 2依赖的方式诱导从人HO-1 E2增强子区域转录的一个正向（5′至3′）eRNA（命名为人HO-1增强子RNA E2 - 3;以下称为eRNA E2-3）的表达。相反，BACH 1（HO-1转录的阻遏物）的敲低进一步增加了DEM诱导的eRNA E2-3转录以及HO-1表达。此外，我们发现eRNA E2-3的敲低选择性地下调DEM诱导的HO-1表达。此外，eRNA E2-3敲低减弱了DEM诱导的Pol II与HO-1的启动子和E2增强子区域的结合，而不影响NRF 2向E2增强子的募集。这些发现表明eRNAE 2 -3是功能性的，并且是HO-1诱导所必需的。
Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation. However, it remains unclear whether eRNAs are involved in the regulation of human heme oxygenase-1 gene (HO-1) induction. Here, we report that multiple nuclear-enriched eRNAs are transcribed from the regions adjacent to two human HO-1 enhancers (i.e. the distal E2 and proximal E1 enhancers), and some of these eRNAs are induced by the oxidative stress-causing reagent diethyl maleate (DEM). We demonstrated that the expression of one forward direction (5′ to 3′) eRNA transcribed from the human HO-1 E2 enhancer region (named human HO-1enhancer RNA E2-3; hereafter called eRNA E2-3) was induced by DEM in an NRF2-dependent manner in HeLa cells. Conversely, knockdown of BACH1, a repressor of HO-1 transcription, further increased DEM-inducible eRNA E2-3 transcription as well as HO-1 expression. In addition, we showed that knockdown of eRNA E2-3 selectively down-regulated DEM-induced HO-1 expression. Furthermore, eRNA E2-3 knockdown attenuated DEM-induced Pol II binding to the promoter and E2 enhancer regions of HO-1 without affecting NRF2 recruitment to the E2 enhancer. These findings indicate that eRNAE2-3 is functional and is required for HO-1 induction.
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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
影响因子：
10.5
作者：
Itoh, K;Wakabayashi, N;Yamamoto, M
通讯作者：
Yamamoto, M
DOI：
10.1016/j.bbamcr.2011.01.008
发表时间：
2011-05
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Khan AA;Quigley JG
通讯作者：
Quigley JG
影响因子：
14.9
作者：
Karolchik D;Barber GP;Casper J;Clawson H;Cline MS;Diekhans M;Dreszer TR;Fujita PA;Guruvadoo L;Haeussler M;Harte RA;Heitner S;Hinrichs AS;Learned K;Lee BT;Li CH;Raney BJ;Rhead B;Rosenbloom KR;Sloan CA;Speir ML;Zweig AS;Haussler D;Kuhn RM;Kent WJ
通讯作者：
Kent WJ
DOI：
10.1006/bbrc.1997.6943
发表时间：
1997-07-18
影响因子：
3.1
作者：
Itoh, K;Chiba, T;Nabeshima, Y
通讯作者：
Nabeshima, Y