Drosophila stem cells share a common requirement for the histone H2B ubiquitin protease scrawny.
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-specific 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 through scny represents a common mechanism within stem cells that is used to repress the premature expression of key differentiation genes, including Notch target genes.
Buszczak
Michael
M
Howard Hughes Medical Institute Research Laboratories, Department of Embryology, Carnegie Institution, Baltimore, MD 21218, USA.
Paterno
Shelley
S
Spradling
Allan C
AC
D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D008297:Male; D008745:Methylation; D009154:Mutation; D051880:Receptors, Notch / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases; D054875:Ubiquitination
D002843:Chromatin; D029721:Drosophila Proteins; D006657:Histones; C497759:N protein, Drosophila; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D010450:Endopeptidases; D064570:Ubiquitin-Specific Proteases; C534688:ubiquitin specific protease 36, Drosophila