title: Expression and function of Set7/9 in pancreatic islets.
abstract: Histone tail acetylation and methylation are known to enhance accessibility of islet genes to transcription factors and the basal transcriptional machinery.  In this brief report, we follow up on a recent study in which we identified the islet enriched factor Set7/9 as a potentially important histone methyltransferase in β-cells (Deering, et al. Diabetes 2009; 58:185-93).  We had suggested that the methylation of H3-Lys4 by Set7/9 enhances accessibility of the insulin gene to the basal transcriptional machinery.  Consistent with this hypothesis, we show here that RNA polymerase II occupancy at the insulin and IAPP genes is considerably enhanced in β-cells compared to α cells (or NIH3T3 cells), and that the converse is true for RNA polymerase II occupancy at the glucagon gene. The enrichment of Set7/9 in β-cells appears to be dependent upon Pdx1, as knockdown of Pdx1 in INS-1 β-cells using small hairpin RNAs almost completely abolishes Set7/9 expression.  A LacZ expression vector driven by the -6.5 kilobase pair Set7/9 promoter that contains putative Pdx1 binding sites shows β-cell-line-specific expression.  Taken together, our data support further the hypothesis that Pdx1-dependent Set7/9 expression may be crucial to enhancing chromatin accessibility and transcription of β-cell genes.
authors.affiliation: Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ogihara
authors.forename: Nathan L
authors.initials: NL
authors.lastname: Vanderford
authors.forename: Bernhard
authors.initials: B
authors.lastname: Maier
authors.forename: Roland W
authors.initials: RW
authors.lastname: Stein
authors.forename: Raghavendra G
authors.initials: RG
authors.lastname: Mirmira
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D055785:Gene Knockdown Techniques; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D007515:Islets of Langerhans / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D041681:NIH 3T3 Cells; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D011495:Histone-Lysine N-Methyltransferase