We are carrying out studies of the histone modifications over the insulin gene locus and its neighborhood in human islet cells, in an attempt to identify long range regulatory influences that may affect insulin gene expression. We have identified an extended domain of open chromatin structure. In addition, we are carrying out measurements of long range physical contacts within the nucleus between the insulin promoter and other genomic sites. We are particularly interested in the possible influence of downstream imprinted loci on insulin expression. We have also collaborated with the laboratory of Dr. Marvin C. Gershengorn in studies of the histone modifications over the insulin locus in human islet-derived precursor cells (hIPCs). We have shown that these cells, although they have lost expression of insulin, retain to a large extend the same modifications found in the active beta cells of islets, strongly supporting the idea that they are poised for expression of insulin. In contrast, other cell types show no such modifications.? ? We are now exploring the long-range interactions between the human insulin locus and other sites in the genome, in order to determine the role of such interactions in insulin gene expression.
| Mutskov, Vesco; Raaka, Bruce M; Felsenfeld, Gary et al. (2007) The human insulin gene displays transcriptionally active epigenetic marks in islet-derived mesenchymal precursor cells in the absence of insulin expression. Stem Cells 25:3223-33 |
