SERPINB2 is regulated by dynamic interactions with pause-release proteins and enhancer RNAs.
SERPINB2 is regulated by dynamic interactions with pause-release proteins and enhancer RNAs.
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DOI：
10.1016/j.molimm.2017.05.005
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发表时间：
2017-08
影响因子：
3.6
通讯作者：
Sullivan KE
中科院分区：
文献类型：
--
作者：
Shii L;Song L;Maurer K;Zhang Z;Sullivan KE
SERPINB 2基因在炎症状态下强烈上调。在单核细胞中，它可以占总细胞蛋白的1%。它的功能是保护免受蛋白毒性应激，并在血管性水肿中发挥作用。本研究的目的是确定嵌入SERPIN基因复合物中的增强子RNA的作用。我们发现，上游增强子RNA上调SERPINB 2，增强子RNA的表达先于SERPINB 2 mRNA的表达。SERPINB 2启动子的研究证明了RNA聚合酶II暂停诱导蛋白NELF的存在。用LPS刺激导致暂停释放激酶P-TEFb的募集和暂停诱导蛋白NELF的离开。RNA免疫沉淀显示NELF和P-TEFb的CDK 9组分在刺激后以不同的动力学与增强子RNA结合。敲低增强子RNA损害了启动子和增强子染色质变化的刺激诱导。相反，过度表达与c-JUN募集增强和SERPINB 2 mRNA表达增加相关。本研究首次将增强子RNA与SERPINB 2相关联，并且首次证明增强子RNA在染色质上获得NELF结合。
The SERPINB2 gene is strongly upregulated in inflammatory states. In monocytes, it can constitute up to 1% of total cellular protein. It functions in protection from proteotoxic stress and plays a role in angioedema. The purpose of this study was to define the roles of enhancer RNAs embedded in the SERPIN gene complex. We found that the upstream enhancer RNAs upregulated SERPINB2 and the enhancer RNAs were expressed prior to those of SERPINB2 mRNA. Studies of the SERPINB2 promoter demonstrated the presence of an RNA polymerase II pause-inducing protein, NELF. Stimulation with LPS led to recruitment of the pause-releasing kinase P-TEFb and departure of the pause-inducing protein NELF. RNA immunoprecipitation revealed that NELF and the CDK9 component of P-TEFb bound to the enhancer RNAs after stimulation with distinct kinetics. Knock-down of the enhancer RNAs compromised stimulus induction of promoter and enhancer chromatin changes. Conversely, over-expression was associated with enhanced recruitment of c-JUN and increased expression of SERPINB2 mRNA expression. This study is the first to associate enhancer RNAs with SERPINB2 and is the first demonstration of acquisition of NELF binding by enhancer RNAs on chromatin.
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影响因子：
4.8
作者：
DICKINSON, JL;BATES, EJ;ANTALIS, TM
通讯作者：
ANTALIS, TM
DOI：
10.1073/pnas.1324151111
发表时间：
2014-05-20
影响因子：
11.1
作者：
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通讯作者：
Kantoff, Philip W.
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64.5
作者：
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通讯作者：
Young, Richard A.
影响因子：
11.4
作者：
BELIN, D;WOHLWEND, A;VASSALLI, JD
通讯作者：
VASSALLI, JD
影响因子：
64.5
作者：
Bose DA;Donahue G;Reinberg D;Shiekhattar R;Bonasio R;Berger SL
通讯作者：
Berger SL