Developmental Biology Select

The role of chromatin regulation in development is the subject of this issue's Developmental Biology Select. Recent discoveries link glycosylation to the repression mediated by Polycomb group proteins and provide insight into a developmental disorder that stems from the loss of a histone methyltransferase. Other work sheds light on particular developmental transitions, including loss of plasticity during embryogenesis, the temporal control of Hox gene expression, and the impact of long-range chromatin interactions on T cell maturation. Polycomb group (PcG) proteins keep key developmental regulators, such as Hox genes, turned off in cells where they must remain inactive. Gambetta et al. (2009) now make the surprising discovery that the PcG gene super sex combs (sxc) in the fruit fly Drosophila encodes a glycosyltransferase. They show that Sxc is the fruit fly homolog of the O-linked N-acetylglucosamine transferase (Ogt) found in vertebrates, which modifies serine and threonine residues with N-acetylglucos-amine (GlcNAc). GlcNAc-modified proteins have in prior work been reported to colocalize with chromatin. Building on this observation, the authors conduct a chromatin immunoprecipitation (ChIP) assay using an antibody that recognizes O-GlcNAc. Of the 1138 sites in the genome that they identify as being occupied by GlcNAc-modified proteins, 490 are at Polycomb response elements bound by the PcG protein Polyhomeotic or the PcG complex PhoRC. The authors further show that Polyhomeotic is a target of GlcNAc modification in vivo. Whether this particular substrate accounts for the effects of loss of Sxc is not yet clear. If it does, future work may determine the mechanism by which GlcNAc modification of Polyhomeotic (or other targets) supports PcG-mediated transcriptional repression. Another interesting angle of PcG-mediated repression that might be explored is the potential impact of glucose availability, which in other settings has been shown to regulate the activity of OGT. Wolf-Hisrchhorn syndrome is a developmental disorder characterized by mental retardation, midline defects, heart malformation, and craniofacial abnormalities. Among the genes potentially involved is Wolf-Hirschhorn syndrome candidate 1 (WHSC1), which is found in a region of the human genome exhibiting hemizygous loss in affected individuals. Nimura et al. (2009) now link the function of mouse Whsc1 to features of the human disease. Whsc1 is a histone H3 lysine 36 (H3K36) trimethyltransferase, and the authors show that loss of Whsc1 decreases the level of H3K36 trimethylation in embryonic stem (ES) cells. In addition, mice deficient in Whsc1 exhibit abnormalities similar to the human syndrome, including heart and midline …