Sex-based eRNA expression and function in ischemic stroke.

Enhancer-derived RNAs (eRNAs) are a new class of long noncoding RNA that have roles in modulating enhancer-mediated gene transcription, which ultimately influences phenotypic outcomes. We recently published the first study mapping genome-wide eRNA expression in the male mouse cortex during ischemic stroke and identified 77 eRNAs that were significantly altered following a 1 h middle cerebral artery occlusion (MCAO) and 6 h of reperfusion, as compared to sham controls. Knockdown of one such stroke-induced eRNA - eRNA_06347 - resulted in significantly larger infarcts, demonstrating a role for eRNA_06347 in modulating the post-stroke pathophysiology in males.

Modulation of Brain Pathology by Enhancer RNAs in Cerebral Ischemia.

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.

Long Noncoding RNAs in the Pathophysiology of Ischemic Stroke.

Ischemic stroke is an acute brain injury with high mortality and disability rates worldwide. The pathophysiological effects of ischemic stroke are driven by a multitude of complex molecular and cellular interactions that ultimately result in brain damage and neurological dysfunction. The Human Genome Project revealed that the vast majority of the human genome (and mammalian genome in general) is transcribed into noncoding RNAs.

Deep Sequencing Reveals Uncharted Isoform Heterogeneity of the Protein-Coding Transcriptome in Cerebral Ischemia.

Gene expression in cerebral ischemia has been a subject of intense investigations for several years. Studies utilizing probe-based high-throughput methodologies such as microarrays have contributed significantly to our existing knowledge but lacked the capacity to dissect the transcriptome in detail. Genome-wide RNA-sequencing (RNA-seq) enables comprehensive examinations of transcriptomes for attributes such as strandedness, alternative splicing, alternative transcription start/stop sites, and sequence composition, thus providing a very detailed account of gene expression.

Discovery of novel stroke-responsive lncRNAs in the mouse cortex using genome-wide RNA-seq.

Long noncoding RNAs (lncRNAs) play major roles in regulating gene expression in mammals, but are poorly understood in ischemic stroke. Using a mouse model of transient focal ischemia, we applied RNA-seq to evaluate for the first time the unbiased, genome-wide expression of lncRNAs as a function of reperfusion time in the cerebral cortex. Focal ischemia was induced in adult male C57BL/6 mice followed by reperfusion for 6, 12 or 24h.

Krüpple-like factors 7 and 6a mRNA expression in adult zebrafish central nervous system.

Krüpple-like factors (KLFs) are transcription factors with zinc finger DNA binding domains known to play important roles in brain development and central nervous system (CNS) regeneration. There is little information on KLFs expression in adult vertebrate CNS. In this study, we used in situ hybridization to examine Klf7 mRNA (klf7) and Klf6a mRNA (klf6a) expression in adult zebrafish CNS.

Differential expression of protocadherin-19, protocadherin-17, and cadherin-6 in adult zebrafish brain.

Cell adhesion molecule cadherins play important roles in both development and maintenance of adult structures. Most studies on cadherin expression have been carried out in developing organisms, but information on cadherin distribution in adult vertebrate brains is limited. In this study we used in situ hybridization to examine mRNA expression of three cadherins, protocadherin-19, protocadherin-17, and cadherin-6 in adult zebrafish brain.

Protocadherin-17 function in Zebrafish retinal development.

Cadherin cell adhesion molecules play crucial roles in vertebrate development including the development of the retina. Most studies have focused on examining functions of classic cadherins (e.g.