Growth retardation and premature aging phenotypes in mice with disruption of the SNF2-like gene, PASG

• DOI: 10.1101/gad.1176104
• Publication Date: 2004-04-27T00:43:27Z
• Authors: Lin-Quan Sun; David W. Lee; Quangeng Zhang; Weihong Xiao; Eric H. Raabe; Alan Meeker; Dengshun Miao; David L. Huso; Robert J. Arceci
• Keywords: Premature aging; Senescence

Imperfect maintenance of genome integrity has been postulated to be an important cause aging. Here we provide support for this hypothesis by demonstrating that the disruption PASG ( lsh ), a SNF2-like factor facilitates DNA methylation, causes global hypomethylation, developmental growth retardation and premature aging phenotype. mutant mice display signs aging, including low birth weight, failure thrive, graying loss hair, reduced skin fat deposition, osteoporosis, kyphosis, cachexia, death. Fibroblasts derived from embryos show replicative senescence Both fibroblasts demonstrate markedly increased expression senescence-associated tumor suppressor genes, such as p16 INK4a , is independent promoter but, instead, associated with down-regulation bmi-1, negative regulator . These studies essential properly maintaining methylation gene patterns are required normal longevity. useful model study well mechanisms regulating epigenetic patterning during development postnatal life.