Methyltransferase Set7/9 Maintains Transcription and Euchromatin Structure at Islet-Enriched Genes

those encoding preproinsulin, requires an appropriate euchroma-tin (or “open”) DNA template characterized by hypermethylation of Lys4 of histone H3. We hypothesized that this modification is maintained in islet -cells by the action of the histone methyl-transferase Set7/9. RESEARCH DESIGN AND METHODS—To identify the role of Set7/9, we characterized its expression pattern and gene regulation and studied its function using RNA interference in both cell lines and primary mouse islets. RESULTS—Within the pancreas, Set7/9 protein shows striking specificity for islet cells, including - and -cells, as well as occasional cells within ducts. Consistent with these findings, the Set7/9 gene promoter contained an islet-specific enhancer lo-cated between 5,768 and 6,030 base pairs (relative to the transcriptional start site) that exhibited Pdx1-responsive activa