Brain development, Chromatin structure, Epigenetics
ATRX is a chromatin remodeling protein of the Snf2 family that participates in diverse cellular functions including regulation of gene expression and chromosome alignment during mitosis and meiosis. Mutations in the human gene cause ATR-X syndrome, a rare disorder characterized by severe cognitive deficits and various developmental abnormalities. Decreased ATRX activity gives rise to severe learning disabilities, indicating a vital role for the development of brain regions involved in learning and memory processing. Conditional inactivation of the Atrx gene in the mouse forebrain leads to neonatal lethality and defective neurogenesis manifested by increased cell death and reduced cellularity in the developing neocortex and hippocampus. Recently, a link has been established between ATRX and the MeCP2 gene product, suggesting that they co-operate to control chromatin structure in brain cells. The study of ATRX and other genetic factors that underlie mental retardation syndromes can significantly contribute to our understanding of brain function and ultimately, human cognition. Our laboratory is currently using mouse and cell culture models to study the outcome of ATRX loss-of-function on chromatin structure, gene expression and cell cycle events.