. Author manuscript; available in PMC: 2014 Jun 2.

Published in final edited form as: Transl Stroke Res. 2013 Jan 8;4(1):56–62. doi: 10.1007/s12975-012-0235-0

Table 1.

Ischemic tolerance targets, sensors, and proteins modified

Epigenetic and cytosolic protein effectors	Physiological state change sensed by the effector	Epigenetic modification
AMP Kinase	High levels of cellular AMP or altered AMP to ATP ratios	Phosphorylation of H2B-Ser³⁶
SCMHI and BMI1, part of the PRC1 polycomb complex	Unknown	Monoubiquitination of H2A and H2B
Jumonji domain histone demethylases	Lowered levels of oxygen, 2-oxoglutarate, vitamin C and cellular iron lead to alterations in histone methylation	Mono, di, and trimethylation of histone N terminal tails (histone H3, lysines 4, 9, 27 36; histone H4 lysine 20)
Zinc Dependent Histone (lysine) deacetylases (Class I and II HDACs)	Inhibited by nitric oxide and dowstream of glutathione depletion	Lysine acetylation on N-terminal tails of histones and transcription factors as well as a an array of cytosolic proteins (e.g., peroxiredoxin)
Sirtuins, NAD+ dependent histone (lysine) deacetylases located in the nucleus, cytoplasm and mitochondria (class III HDACs)	Altered NAD+/NADH ratio or consumption of NAD+	Lysine acetylation on N-terminal tails of histones and transcription factors. Lysine malonylation and succinylation in mitochondria