The enhancer code underlying astrocytes-specific inflammatory transcriptional responses

In response to injury or disease, functional changes in astrocytes can be detrimental to neural repair and contribute to the progression of neuroinflammatory conditions. While studies have characterized the gene expression programs activated in astrocytes during neuroinflammation, the gene regulatory mechanisms underlying proinflammatory responses in astrocytes remain largely unknown.

We addressed this knowledge gap by annotating genomic enhancers in primary mouse astrocytes and examining their transcriptional activation in response to interleukin-1 beta (IL-1β), a proinflammatory cytokine. Capped small RNA sequencing (csRNA-seq) was employed to profile transcription initiation activity at cis-regulatory elements, allowing for the identification of 176,743 Transcriptional Start Regions (TSRs). These TSRs were distributed mainly in distal enhancer regulatory regions associated with enhancer (e)RNA production.