Histone Methylation Silences Genes

Researchers have established a link between histone methylation and Polycomb group proteins (PcG)-mediated gene silencing in the developing embryo. This finding was reported in the November 1, 2002, issue of Science.

Gene silencing is crucial for normal embryonic development. When the developing embryo no longer requires the products of a particular gene, that gene must be permanently turned off (silenced). The Hox genes, which are expressed in early embryonic development and then silenced by the action of proteins produced by the Polycomb group of genes, have been of particular interest. Embryos from animals with mutated or missing Polycomb genes fail to silence the Hox genes, and the embryos do not develop normally.

In the current study, investigators from the University of North Carolina School of Medicine (Chapel Hill, USA) described the purification and characterization of a Polycomb group protein complex. "Basically, we found that the Polycomb proteins function through methylating a particular lysine residue, lysine 27, on histone 3,” explained senior author Dr. Yi Zhang, UNC assistant professor of biochemistry and biophysics.

When enzyme activity causing methylation of this site is blocked, Hox gene silencing does not occur. The permanent silencing of the Hox genes was explained by the observation that histone methylation cannot be reversed. In Dr. Zhang's words, "Thus far, no ‘histone demethylase' has been discovered.”



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Univ. of NC School of Medicine