The evolution of the type I IFN transcriptional response across human populations [PRO-seq]

Type I interferon cytokines trigger an antiviral cellular state by binding to membrane receptors, encoded in chromosome 21, that transduce a signaling response to induce the transcription of hundreds of interferon-stimulated genes. However, it remains poorly understood how gene transcription regulation has been rewired through evolutionary time, even at relatively short time scales, to achieve inter- and intra-species variation in interferon-controlled changes in gene expression.

We generated nascent transcription (PRO-seq) and steady-state mRNA expression (RNA-seq) datasets from human individuals from diverse ethnic backgrounds, and from individuals with trisomy 21, to investigate differences in the transcriptional response triggered by type I interferon within human populations, and to study the interferonopathy related to trisomy 21.