ArticleHuman molecular genetics2008
Three-dimensional conformation at the H19/Igf2 locus supports a model of enhancer tracking.
Article in Human molecular genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- Aberrant Enhancer Regulation, Phase Separation, and Autoimmune Diseases.Clinical reviews in allergy & immunology · 2025Review
- Deletion of a single CTCF motif at the boundary of a chromatin domain with three FGF genes disrupts gene expression and embryonic development.Developmental cell · 2025Article
- Widespread allele-specific topological domains in the human genome are not confined to imprinted gene clusters.Genome biology · 2023Article
- Enhancer-promoter interactions can bypass CTCF-mediated boundaries and contribute to phenotypic robustness.Nature genetics · 2023Article
- Control of enhancer and promoter activation in the type I interferon response by the histone demethylase Kdm4d/JMJD2d.Frontiers in immunology · 2023Article
- Tissue-specific Grb10/Ddc insulator drives allelic architecture for cardiac development.Molecular cell · 2022Article
- Orientation of mouse H19 ICR affects imprinted H19 gene expression through promoter methylation-dependent and -independent mechanisms.Communications biology · 2021Article
- Review
- Decreased Enhancer-Promoter Proximity Accompanying Enhancer Activation.Molecular cell · 2019Article
- H19 is not hypomethylated or upregulated with age or sex in the aortic valves of mice.Physiological reports · 2019Article
- CTCF-Induced Circular DNA Complexes Observed by Atomic Force Microscopy.Journal of molecular biology · 2018Article
- Humanized H19/Igf2 locus reveals diverged imprinting mechanism between mouse and human and reflects Silver-Russell syndrome phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Kaiso mediates human ICR1 methylation maintenance and H19 transcriptional fine regulation.Clinical epigenetics · 2016Article
- Influence of a CTCF-Dependent Insulator on Multiple Aspects of Enhancer-Mediated Chromatin Organization.Molecular and cellular biology · 2015Article
- CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation.Nucleic acids research · 2014Article
- Promoter histone H3K27 methylation in the control of IGF2 imprinting in human tumor cell lines.Human molecular genetics · 2014Article
- Oct4/Sox2 binding sites contribute to maintaining hypomethylation of the maternal igf2/h19 imprinting control region.PloS one · 2013Article
- Cohesin regulates tissue-specific expression by stabilizing highly occupied cis-regulatory modules.Genome research · 2012Article
- An ectopic CTCF-dependent transcriptional insulator influences the choice of Vβ gene segments for VDJ recombination at TCRβ locus.Nucleic acids research · 2012Article
- Identification of a DNA methylation-independent imprinting control region at the Arabidopsis MEDEA locus.Genes & development · 2012Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Insight into how the mammalian genome is structured in vivo is key to understanding transcriptional regulation. This is especially true in complex domains in which genes are coordinately regulated by long-range interactions between cis-regulatory elements. The regulation of the H19/Igf2 imprinted region depends on the presence of several cis-acting sequences, including a methylation-sensitive insulator between Igf2 and H19 and shared enhancers downstream of H19. Each parental allele has a distinct expression pattern. We used chromosome conformation capture to assay the native three-dimensional organization of the H19/Igf2 locus on each parental copy. Furthermore, we compared wild-type chromosomes to several mutations that affect the insulator. Our results show that promoters and enhancers reproducibly co-localize at transcriptionally active genes, i.e. the endodermal enhancers contact the maternal H19 and the paternal Igf2 genes. The active insulator blocks traffic of the enhancers along the chromosome, restricting them to the H19 promoter. Conversely, the methylated inactive insulator allows the enhancers to contact the upstream regions, including Igf2. Mutations that either remove or inhibit insulator activity allow unrestricted access of the enhancers to the whole region. A mutation that allows establishment of an enhancer-blocker on the normally inactive paternal copy diminishes the contact of the enhancer with the Igf2 gene. Based on our results, we propose that physical proximity of cis-acting DNA elements is vital for their activity in vivo. We suggest that enhancers track along the chromosome until they find a suitable promoter sequence to interact with and that insulator elements block further tracking of enhancers.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.