Neuroscience Individuals suffering a stroke show various degrees of neurological dysfunction due to brain tissue that has been deprived of oxygen. Strategies to minimize damage from this common problem are needed, and this has focused the attention of investigators on a process whereby the resistance of neurons to ischemia (or loss of blood flow) is increased if cells have been exposed previously to a mild bout of ischemia insufficient to cause permanent damage. Stapels et al. conducted a systematic search for proteins that showed increased abundance in such resistant neurons and identified SCMH1, a mouse homolog of a Drosophila polycomb group protein. SCMH1 can modify histones and is thought to function by repressing transcription. In a mouse neuroblastoma cell line, depletion of SCMH1 diminished the induction of tolerance to ischemia, and overexpression of SCMH1 promoted tolerance even in the absence of a conditioning ischemic event. SCMH1 associates with the promoters of two potassium ion–channel genes, and inhibiting the transcription of these genes was sufficient to produce tolerance to subsequent ischemia. Sci. Sig. 3 , ra15 (2010).