Chromatin modification of the human imprinted NDN (necdin) gene detected by in vivo footprinting.
Allele-specific transcription is a characteristic feature of imprinted genes. Many imprinted genes are also transcribed in a tissue- or cell type-specific manner. Overlapping epigenetic signals must, therefore, modulate allele-specific and tissue-specific expression at imprinted loci. In addition, long-range interactions with an Imprinting Center (IC) may influence transcription, in an allele-specific or cell-type specific manner. The IC on human chromosome 15q11 controls parent-of-origin specific allelic identity of a set of genes located in cis configuration within 2 Mb. We have now examined the chromatin accessibility of the promoter region of one of the Imprinting Centre-controlled genes, NDN encoding necdin, using in vivo DNA footprinting to identify sites of DNA-protein interaction and altered chromatin configuration. We identified sites of modified chromatin that mark the parental alleles in NDN-expressing cells, and in cells in which NDN is not expressed. Our results suggest that long-lasting allele-specific marks and more labile tissue-specific marks layer epigenetic information that can be discriminated using DNA footprinting methodologies. Sites of modified chromatin mark the parental alleles in NDN-expressing cells, and in cells in which NDN is not expressed. Our results suggest that a layering of epigenetic information controls allele- and tissue-specific gene expression of this imprinted gene.
Hanel
Meredith L
ML
Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
Lau
Jason C Y
JC
Paradis
Isabelle
I
Drouin
Régen
R
Wevrick
Rachel
R
D001483:Base Sequence; D002843:Chromatin / Q000737:chemistry*; D004247:DNA; D018983:DNA Footprinting; D018392:Genomic Imprinting; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic
D002843:Chromatin; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C069766:necdin; D004247:DNA