Brona McVittie reports :: February 2007

In any of the billions of cells in your body, most of your genes are silenced. The small number of active genes in any one cell determines their personality. Brain cells behave differently to cells that line our gut, for example, owing to different active gangs of genes. Keeping most of the genome silent is a job done by memory marks on top of the DNA sequence (DNA methylation) and on the proteins that package up our chromosomes (histone modifications). Scientists have identified enzymes that lay down memory marks on DNA, which switches genes off, but aren’t yet clear exactly how genes get switched on. What rubs off these repressive memory marks?

Frank Lyko and colleagues in a letter to Nature describe a protein called Gadd45-alpha, which seems to be involved in awakening genes by stripping silencers off the genome. The authors reckon that Gadd45-alpha promotes the process of DNA repair, which can wipe off methylation marks, potentially switching genes on. Upping the levels of this protein in frog eggs strips DNA of memory marks, but low levels of the protein seem to increase DNA methylation across the whole genome.