• X chromosome escapee genes are involved in ischemic sexual dimorphism through epigenetic modification of inflammatory signals

      Qi, Shaohua; Al Mamun, Abdullah; Ngwa, Conelius; Romana, Sharmeen; Ritzel, Rodney; Arnold, Arthur P; McCullough, Louise D; Liu, Fudong (Springer Nature, 2021-03-12)
      Stroke is a sexually dimorphic disease. Previous studies have found that young females are protected against ischemia compared to males, partially due to the protective effect of ovarian hormones, particularly estrogen (E2). However, there are also genetic and epigenetic effects of X chromosome dosage that contribute to stroke sensitivity and neuroinflammation after injury, especially in the aged. Genes that escape from X chromosome inactivation (XCI) contribute to sex-specific phenotypes in many disorders. Kdm5c and kdm6a are X escapee genes that demethylate H3K4me3 and H3K27me3, respectively. We hypothesized that the two demethylases play critical roles in mediating the stroke sensitivity.