Readthrough transcription: How are DoGs made and what do they do?

In recent years, the realization that most of the genome is transcribed has transformed the study of mammalian gene expression. Much effort has gone into investigating how this pervasive transcription is regulated and what the functions of the resulting transcripts are, if any. We recently discovered that stress-induced transcriptional readthrough generates very long downstream of gene containing transcripts (DoGs), which may explain up to 20% of intergenic transcription. DoGs are induced by osmotic stress at the level of transcription by a mechanism that depends on calcium release from the endoplasmic reticulum mediated by IP3 receptors. Here, we discuss DoG induction and function in the context of the literature, with special focus on 2 outstanding questions. First, we discuss possible molecular mechanisms underlying DoG induction through reduced transcription termination. Second, we explore how DoGs may function in maintaining euchromatin after nuclear scaffold stress. In short, we review important aspects of DoG biogenesis and function, and provide an outlook for continued DoG study.