Modulation of Brain Pathology by Enhancer RNAs in Cerebral Ischemia
| Autor: | Ashutosh Dharap, Sunil Bhattarai, Atish Gandhi, Aparna Akella |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Neurology Transcription Genetic Neuroscience (miscellaneous) Ischemia Brain damage Biology Neuroprotection Article Brain Ischemia 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Downregulation and upregulation medicine Animals cardiovascular diseases Enhancer Ischemic Stroke Cerebral Cortex Gene knockdown Genome Brain medicine.disease Phenotype Chromatin Mice Inbred C57BL Enhancer Elements Genetic 030104 developmental biology RNA Female medicine.symptom Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Mol Neurobiol |
| ISSN: | 1559-1182 0893-7648 |
| DOI: | 10.1007/s12035-020-02194-9 |
| Popis: | 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. The 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. |
| Databáze: | OpenAIRE |
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