Modulation of Brain Pathology by Enhancer RNAs in Cerebral Ischemia.
Modulation of Brain Pathology by Enhancer RNAs in Cerebral Ischemia.
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DOI：
10.1007/s12035-020-02194-9
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发表时间：
2021-04
影响因子：
5.1
通讯作者：
Dharap A
中科院分区：
文献类型：
--
作者：
Bhattarai S;Akella A;Gandhi A;Dharap A
最近的研究报道了哺乳动物增强子广泛的刺激依赖性转录为非编码增强子rna (erna)，其中一些在增强子介导的靶基因诱导和发育和疾病期间表型结果的调节中起核心作用。在脑缺血中，erna的表达和功能几乎是未知的。在这里，我们应用全基因组H3K27ac ChIP-seq和全基因组RNA-seq分别鉴定短暂局灶性缺血小鼠大脑皮层中的增强子元件和卒中诱导的erna。在大脑中动脉闭塞（MCAO） 1小时和再灌注6小时后，我们发现，与假手术相比，卒中中有77个erna显著上调，其中55个erna在卒中中完全表达。与对照组相比，敲低小鼠大脑中两种脑卒中诱导的erna导致梗死体积显著增大，这表明这些erna参与脑卒中后的神经保护反应。对男性和女性大脑皮层eRNA表达的初步比较揭示了性别依赖模式，这可能是两性对中风反应的生理差异的基础。总之，这项研究首次阐明了脑卒中后皮层的eRNA景观，并证明了eRNA在调节脑卒中后皮层脑损伤中的重要性。
Recent studies have reported widespread stimulus-dependent transcription of mammalian enhancers into noncoding enhancer RNAs (eRNAs), some of which have central roles in the enhancer-mediated induction of target genes and modulation of phenotypic outcomes during development and disease. In cerebral ischemia, the expression and functions of eRNAs are virtually unknown. Here, we applied genome-wide H3K27ac ChIP-seq and genome-wide RNA-seq to identify enhancer elements and stroke-induced eRNAs, respectively, in the mouse cerebral cortex during transient focal ischemia. Following a 1 h middle cerebral artery occlusion (MCAO) and 6 h of reperfusion, we identified 77 eRNAs that were significantly upregulated in stroke as compared to sham, of which 55 were exclusively expressed in stroke. Knockdown of two stroke-induced eRNAs in the mouse brain resulted in significantly larger infarct volumes as compared to controls, suggesting that these eRNAs are involved in the post-stroke neuroprotective response. A preliminary comparison of eRNA expression in the male versus female cortices revealed sex-dependent patterns that may underlie the physiological differences in response to stroke between the two sexes. Together, this study is the first to illuminate the eRNA landscape in the post-stroke cortex and demonstrate the significance of an eRNA in modulating post-stroke cortical brain damage.
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影响因子：
16.8
作者：
Werner MS;Sullivan MA;Shah RN;Nadadur RD;Grzybowski AT;Galat V;Moskowitz IP;Ruthenburg AJ
通讯作者：
Ruthenburg AJ
影响因子：
64.5
作者：
Bhatt DM;Pandya-Jones A;Tong AJ;Barozzi I;Lissner MM;Natoli G;Black DL;Smale ST
通讯作者：
Smale ST
影响因子：
64.8
作者：
Lai F;Gardini A;Zhang A;Shiekhattar R
通讯作者：
Shiekhattar R
DOI：
10.1073/pnas.1324151111
发表时间：
2014-05-20
影响因子：
11.1
作者：
Hsieh, Chen-Lin;Fei, Teng;Kantoff, Philip W.
通讯作者：
Kantoff, Philip W.
影响因子：
16
作者：
Kaikkonen, Minna U.;Spann, Nathanael J.;Heinz, Sven;Romanoski, Casey E.;Allison, Karmel A.;Stender, Joshua D.;Chun, Hyun B.;Tough, David F.;Prinjha, Rab K.;Benner, Christopher;Glass, Christopher K.
通讯作者：
Glass, Christopher K.