AI Article Synopsis
- The regulation of H19 and Igf2 gene imprinting relies on shared elements identified through human and mouse comparative analysis.
- Transgene experiments showed that specific regions 3' of the H19 gene, including endodermal enhancers, play a key role in this regulatory process.
- Despite mutations to these enhancers and a 4.2-kb region, H19 and Igf2 expression patterns were mostly preserved, indicating other factors may compensate for the loss of these conserved elements.
Article Abstract
The regulation of H19 and Igf2 imprinting and expression depends on common elements. Using comparative analysis between human and mouse, we identified conserved regions 3' of the H19 transcription unit, including the H19/Igf2 endodermal enhancers and elements within a 4.2-kb domain between the H19 transcription unit and the enhancers. Transgene experiments implicate these elements in imprinting regulation. To establish whether they are required at the endogenous locus, first we replaced the endodermal enhancers with the alpha-fetoprotein endodermal enhancers (H19Afp). Second, we deleted the 4.2-kb region (H19delta4.2). Our analysis revealed that H19 and Igf2 imprinting and tissue-specific expression were maintained for both mutations, except for a slight reduction in paternal Igf2 expression from the H19Afp allele in liver. These results demonstrate that the H19 insulator can interact with heterologous enhancers to imprint Igf2. Furthermore, for H19, chromatin context or additional sequences possibly compensate for loss of conserved 3' elements.
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| http://dx.doi.org/10.1016/j.ygeno.2003.12.001 | DOI Listing |
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