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Expression and Function of Set7/9 in Pancreatic Islets

Takeshi Ogihara, Nathan L. Vanderford, Bernhard Maier, Roland W. Stein and Raghavendra G. Mirmira

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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.

Deering, TG, Ogihara, T, Trace, AP, Maier, B, Mirmira, RG. Methyltransferase Set7/9 maintains transcription and euchromatin structure at islet-enriched genes. Diabetes 2009; 58:185-93

Authors

Takeshi Ogihara

Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN USA

Nathan L. Vanderford

Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN USA

Bernhard Maier

Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN USA

Roland W. Stein

Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN USA

Raghavendra G. Mirmira Corresponding author: mirmira@iupui.edu

Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN USA

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.