Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha.
Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha.
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DOI：
10.1093/nar/gks409
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发表时间：
2012-08
影响因子：
14.9
通讯作者：
Bell DA
中科院分区：
文献类型：
--
作者：
Chorley BN;Campbell MR;Wang X;Karaca M;Sambandan D;Bangura F;Xue P;Pi J;Kleeberger SR;Bell DA
在哺乳动物中，细胞氧化和亲电应激触发由NRF2(核因子（红细胞衍生）2样；NFE2L2)与应激反应基因附近的脱氧核糖核酸调控序列结合。对NRF2缺陷小鼠的研究表明，数百个基因可能受NRF2调控。为了鉴定人类nrf2调控基因，我们对经膳食异硫氰酸盐、萝卜硫素（SFN）处理的淋巴样细胞进行了染色质免疫沉淀（ChIP）测序实验，并对候选细胞进行了后续生物学实验。我们发现242个高置信度nrf2结合的基因组区域，其中96%的区域含有nrf2调控序列基序。大多数结合位点靠近NRF2通路的潜在新成员。利用平行芯片技术和nrf2沉默细胞系对选定的候选基因进行验证表明，大约三分之二的候选基因的表达可能直接依赖于nrf2，包括类视黄醛X受体α (RXRA)。NRF2调控RXRA对类视黄醇治疗和脂肪形成的反应有影响。在小鼠中，3T3-L1细胞SFN处理在脂肪形成早期影响Rxra的表达，并抑制nrf2延迟的Rxra表达，导致脂肪形成受损。
Cellular oxidative and electrophilic stress triggers a protective response in mammals regulated by NRF2 (nuclear factor (erythroid-derived) 2-like; NFE2L2) binding to deoxyribonucleic acid-regulatory sequences near stress-responsive genes. Studies using Nrf2-deficient mice suggest that hundreds of genes may be regulated by NRF2. To identify human NRF2-regulated genes, we conducted chromatin immunoprecipitation (ChIP)-sequencing experiments in lymphoid cells treated with the dietary isothiocyanate, sulforaphane (SFN) and carried out follow-up biological experiments on candidates. We found 242 high confidence, NRF2-bound genomic regions and 96% of these regions contained NRF2-regulatory sequence motifs. The majority of binding sites were near potential novel members of the NRF2 pathway. Validation of selected candidate genes using parallel ChIP techniques and in NRF2-silenced cell lines indicated that the expression of about two-thirds of the candidates are likely to be directly NRF2-dependent including retinoid X receptor alpha (RXRA). NRF2 regulation of RXRA has implications for response to retinoid treatments and adipogenesis. In mouse, 3T3-L1 cells’ SFN treatment affected Rxra expression early in adipogenesis, and knockdown of Nrf2-delayed Rxra expression, both leading to impaired adipogenesis.
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影响因子：
4.5
作者：
Choy E;Yelensky R;Bonakdar S;Plenge RM;Saxena R;De Jager PL;Shaw SY;Wolfish CS;Slavik JM;Cotsapas C;Rivas M;Dermitzakis ET;Cahir-McFarland E;Kieff E;Hafler D;Daly MJ;Altshuler D
通讯作者：
Altshuler D
影响因子：
3.8
作者：
Cho, Hye-Youn;Kleeberger, Steven R.
通讯作者：
Kleeberger, Steven R.
影响因子：
4.8
作者：
Erickson, AM;Nevarea, Z;Mulcahy, RT
通讯作者：
Mulcahy, RT
DOI：
10.1164/rccm.200907-1047oc
发表时间：
2010-07-01
影响因子：
24.7
作者：
Cho, Hye-Youn;Gladwell, Wesley;Kleeberger, Steven R.
通讯作者：
Kleeberger, Steven R.
影响因子：
1.6
作者：
Franzini, Aldo;Picozzi, Stefano Carlo Maria;Leone, Biagio Eugenio
通讯作者：
Leone, Biagio Eugenio