Friday, January 9, 2009

Drosophila Stem Cells Share a Common Requirement for the Histone H2B Ubiquitin Protease Scrawny

Buszczak M, Paterno S, Spradling AC.

Present address: UT Southwestern Medical Center, Department of Molecular Biology, Dallas, TX 75390, USA.; Howard Hughes Medical Institute Research Laboratories, Department of Embryology, Carnegie Institution of Washington, Baltimore, MD 21218, USA.

Stem cells within diverse tissues share the need for a chromatin configuration that promotes self-renewal, yet few chromatin proteins are known to regulate multiple types of stem cells. We describe a Drosophila gene, scrawny (scny), encoding a ubiquitin protease, which is required in germline, epithelial, and intestinal stem cells. Like its yeast relative UBP10, Scrawny deubiquitylates histone H2B and functions in gene silencing. Consistent with previous studies of this conserved pathway of chromatin regulation, scny mutant cells have elevated levels of ubiquitinylated H2B and trimethylated H3K4. Our findings suggest that inhibiting H2B ubiquitylation via scny represents a common mechanism within stem cells that is used to repress the premature expression of key differentiation genes, including Notch target genes.

As commented in Science: "Ubiquitination of one of the histones, H2B, has consequences for modifications such as methylation of other histones. These interactions cascade down to control the general activity of the genes bound up with these histones. Buszczak et al. show that in Drosophila, a ubiquitin protease, scrawny, helps keep genes silent. Scrawny's functions seem particularly important for stem cells in the germline, in epithelia, and in the intestine. In various types of stem cells, the balance between stem and differentiated fates might be tipped by a common chromatin modification route".