H19-ICR H19/IGF2 imprinting control region
Gene ID: 105259599, updated on 27-Aug-2024Gene type: biological region
Also known as: BWS; IC1; WT2; ICR1; SRS1; H19-DMD; ICR1-DMR
Summary
This region includes a methylation-sensitive enhancer-blocking element that controls imprinted expression of the non-coding H19 gene and the gene encoding insulin-like growth factor 2 (IGF2). These neighboring genes exist in a head-to-tail arrangement in opposite orientations and share an enhancer, but the H19 gene is only expressed from the maternal allele, while the IGF2 gene is only expressed from the paternal allele. This element, which is a differentially methylated region (DMR), is located just upstream of the H19 gene. It is unmethylated on the maternal allele, which permits binding of the CTCF protein, and it can thus function as an enhancer-blocking element to prevent activation of IGF2 by the enhancer, thereby allowing H19 activation. However, it is methylated on the paternal allele and CTCF cannot bind, thus allowing the enhancer to activate the IGF2 gene, and the H19 gene is silenced. This DMR includes multiple direct repeat units and seven CTCF-binding sites. Four subregions were shown to be active enhancers by ChIP-STARR-seq in human embryonic stem cells, where all are marked by the H3K27ac and H3K4me1 histone modifications, with three being additionally associated with the NANOG transcription factor and two are also associated with OCT4. Mutations in this genomic region are a cause of Wilms tumor, and also Beckwith-Wiedemann syndrome through either a gain or loss of methylation. This element has also been implicated in dysregulated H19-IGF2 imprinting found in osteosarcoma and in Silver-Russell syndrome. [provided by RefSeq, Nov 2022]
Associated conditions
Genomic context
- Location:
- 11p15.5
- Sequence:
- Chromosome: 11; NC_000011.10 (1998202..2003509)
- Total number of exons:
- 0
Variation
Resource | Links for this gene |
---|---|
ClinVar | Variants reported to ClinVar |
SNP | Variation Viewer for H19-ICR variants |
Genome viewer | Explore NCBI-annotated and select non-NCBI annotated genome assemblies |
- ClinVarRelated medical variations
- MedGenRelated information in MedGen
- OMIMLink to related OMIM entry
- PubMed (OMIM)Gene links to PubMed derived from omim_pubmed_cited links
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