Ischemic stroke altered the expression profiles of super enhancer RNAs in mouse brain in a sexually dimorphic manner

Abstract

Super enhancer RNAs (seRNAs) serve as vital regulators of gene expression, yet their role in ischemic stroke remains unexplored. Using microarrays, we profiled seRNAs and their target mRNAs in the peri-infarct cortex of male and female C57BL/6 J mice at 6 h and 24 h of reperfusion after transient focal ischemia. The seRNA expression profiles altered in a temporal and sex-specific manner with a more pronounced dysregulation in males. Gene ontology analysis showed that stroke-responsive seRNA-associated mRNAs involved in critical pathways, including neurogenesis, angiogenesis, and immune responses. Weighted Gene Co-expression Network Analysis showed that the upregulated driver seRNAs are associated with leukocyte proliferation and inflammation, and the downregulated driver seRNAs are linked to nucleosome organization, RNA stability, neuronal apoptosis, and mTOR signaling after focal ischemia. Several stroke-responsive seRNAs are also observed to be associated with transcription factors. These results suggest that seRNAs are pivotal regulators of post-stroke brain damage and recovery, providing potential targets for therapeutic intervention.

Keywords: Brain damage; Epigenetic regulation; Neuroinflammation; Noncoding RNAs; Transcription; seRNAs.