H19-ICR H19/IGF2 imprinting control region [Homo sapiens (human)] - Gene

Summary

Gene symbol: H19-ICR
Gene description: H19/IGF2 imprinting control region
Primary source: MIM:616186
Gene type: biological region
Feature type(s): protein_bind
regulatory: enhancer, enhancer_blocking_element, imprinting_control_region
repeat_region
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
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]
Orthologs: mouse all
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Genomic context

Location:: 11p15.5

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (1998202..2003509)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (2085879..2091186)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (2019975..2024739)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Transient establishment of imprinted DNA methylation of transgenic human IC1 sequence in mouse during the preimplantation period.
Title: Transient establishment of imprinted DNA methylation of transgenic human IC1 sequence in mouse during the preimplantation period.
Results show that Kaiso binding to unmethylated Kaiso binding site in the human ICR1 is necessary for ICR1 methylation maintenance and affects transcription rates of the lncRNA H19.
Title: Kaiso mediates human ICR1 methylation maintenance and H19 transcriptional fine regulation.
These results confirm the crucial role of loss of imprinting at the IGF2H19 DMR in the pathogenesis of rhabdomyosarcoma
Title: 5‑Azacytidine inhibits human rhabdomyosarcoma cell growth by downregulating insulin‑like growth factor 2 expression and reactivating the H19 gene product miR‑675, which negatively affects insulin‑like growth factors and insulin signaling.
Exhaustive methylation analysis revealed uneven profiles of methylation at IGF2/ICR1/H19 11p15 loci in Russell Silver syndrome.
Title: Exhaustive methylation analysis revealed uneven profiles of methylation at IGF2/ICR1/H19 11p15 loci in Russell Silver syndrome.

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Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Beckwith-Wiedemann syndrome MedGen: C0004903 OMIM: 130650 GeneReviews: Wilms Tumor Predisposition, Beckwith-Wiedemann Syndrome	Compare labs
Silver-Russell syndrome 1 MedGen: C5393125 OMIM: 180860 GeneReviews: Silver-Russell Syndrome	Compare labs
Wilms tumor 2 MedGen: C3887743 OMIM: 194071 GeneReviews: Wilms Tumor Predisposition	Compare labs

Variation

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See variants in ClinVar

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General gene information

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Other Names

H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2019432-2020280
ICR1 differentially methylated region
NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2020281-2021127
OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2021977-2022824
OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2022825-2023672
imprinting center 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.