Conserved DNA methylation in Gadd45a(-/-) mice.

Gadd45a (growth arrest and DNA-damage-inducible protein 45 alpha) plays a pivotal role in cellular stress responses and is implicated in DNA repair, cell cycle arrest and apoptosis.(1) Recently, it was proposed that GADD45A is a key regulator of active DNA demethylation by way of its role in DNA repair.(2) Barreto et al. reported that Gadd45a overexpression activated transcription from methylation-silenced reporter plasmids and promoted global DNA demethylation. siRNA-mediated knockdown of Gadd45a levels resulted in increased levels of DNA methylation at specific endogenous loci. Based on these exciting results, Gadd45a(-/-) mice might be predicted to have a hypermethylation phenotype. We report here that neither global nor locus-specific methylation is increased in Gadd45a(-/-) mice.