RT Journal Article
SR Electronic
T1 Polycomb Group Proteins as Epigenetic Mediators of Neuroprotection in Ischemic Tolerance
JF Science Signaling
JO Sci. Signal.
FD American Association for the Advancement of Science
SP ra15
OP ra15
DO 10.1126/scisignal.2000502
VO 3
IS 111
A1 Stapels, Martha
A1 Piper, Chelsea
A1 Yang, Tao
A1 Li, Minghua
A1 Stowell, Cheri
A1 Xiong, Zhi-gang
A1 Saugstad, Julie
A1 Simon, Roger P.
A1 Geromanos, Scott
A1 Langridge, James
A1 Lan, Jing-quan
A1 Zhou, An
YR 2010
UL http://stke.sciencemag.org/content/3/111/ra15.abstract
AB Exposing the brain to sublethal ischemia affects the response to a subsequent, otherwise injurious ischemia, resulting in transcriptional suppression and neuroprotection, a response called ischemic tolerance. Here, we show that the proteomic signature of the ischemic-tolerant brain is characterized by increased abundance of transcriptional repressors, particularly polycomb group (PcG) proteins. Knocking down PcG proteins precluded the induction of ischemic tolerance, whereas in an in vitro model, overexpressing the PcG proteins SCMH1 or BMI1 induced tolerance to ischemia without preconditioning. We found that PcG proteins are associated with the promoter regions of genes encoding two potassium channel proteins that show decreased abundance in ischemic-tolerant brains. Furthermore, PcG proteins decreased potassium currents in cultured neuronal cells, and knocking down potassium channels elicited tolerance without preconditioning. These findings reveal a previously unknown mechanism of neuroprotection that involves gene repressors of the PcG family.