The 5' flank of mouse H19 in an unusual chromatin conformation unidirectionally blocks enhancer-promoter communication

C. Kanduri, C. Holmgren, M. Pilartz, G. Franklin, M. Kanduri, L. Liu, V. Ginjala, E. Ullerås, R. Mattsson, R. Ohlsson

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)449-457
Number of pages9
JournalCurrent Biology
Issue number8
StatePublished - Apr 1 2000
Externally publishedYes

Bibliographical note

Funding Information:
We acknowledge valuable advice by örjan Wrange, Andras Paldi and Vincenzo Pirotta. We also thank Anita Mattsson for excellent technical assistance. We are grateful for initial technical assistance by Niklas Holmström and Fredrik Åberg. This work was supported by the Natural Science Research Council (NFR), the Swedish Cancer Research Foundation (RmC/CF) and the Swedish Pediatric Cancer Foundation (BCF).


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