The 5' flank of mouse H19 in an unusual chromatin conformation unidirectionally blocks enhancer-promoter communication
| Autor: | Chandra Kanduri, Rolf Ohlsson, Vasudeva Ginjala, Gary C. Franklin, Marcel Pilartz, Claes Holmgren, Ragnar Mattsson, Liang Liu, Erik Ullerås, Meena Kanduri |
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| Rok vydání: | 2000 |
| Předmět: |
Male
RNA Untranslated Somatic cell Protein Conformation Muscle Proteins Biology Polymerase Chain Reaction General Biochemistry Genetics and Molecular Biology Cell Line Mice Fetus Transformation Genetic Insulin-Like Growth Factor II Nucleosome Animals Humans Allele Enhancer Promoter Regions Genetic Psychological repression Gene Alleles Genetics Agricultural and Biological Sciences(all) Biochemistry Genetics and Molecular Biology(all) Terminal Repeat Sequences female genital diseases and pregnancy complications Chromatin Blotting Southern Enhancer Elements Genetic embryonic structures Female RNA Long Noncoding General Agricultural and Biological Sciences Minigene Plasmids |
| Zdroj: | Current biology : CB. 10(8) |
| ISSN: | 0960-9822 |
| Popis: | Background: During mouse prenatal development, the neighbouring insulin-like growth factor II ( Igf2 ) and H19 loci are expressed monoallelically from the paternal and maternal alleles, respectively. Identical spatiotemporal expression patterns and enhancer deletion experiments show that the Igf2 and H19 genes share a common set of enhancers. Deletion of a differentially methylated region in the 5′ flank of the H19 gene partially relieves the repression of the maternal Igf2 and paternal H19 alleles in the soma. The mechanisms underlying the function of the 5′ flank of the H19 gene are, however, unknown. Results: Chromatin analysis showed that the 5′ flank of the mouse H19 gene contains maternal-specific, multiple nuclease hypersensitive sites that map to linker regions between positioned nucleosomes. These features could be recapitulated in an episomal-based H19 minigene, which was propagated in human somatic cells. Although the 5′ flank of the H19 promoter has no intrinsic silencer activity under these conditions, it unidirectionally extinguished promoter–enhancer communications in a position-dependent manner, without directly affecting the enhancer function. Conclusions: The unmethylated 5′ flank of the H19 gene adopts an unusual and maternal-specific chromatin conformation in somatic cells and regulates enhancer–promoter communications, thereby providing an explanation for its role in manifesting the repressed state of the maternally inherited Igf2 allele. |
| Databáze: | OpenAIRE |
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