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Updated: May 27, 2026

Chromatin Isolation by RNA Purification (ChIRP)
Published on: March 25, 2012
Enhancer-driven chromatin interactions during development promote escape from silencing by a long non-coding RNA
Lisa Korostowski1, Anjali Raval, Gillian Breuer
1Fels Institute for Cancer Research & Molecular Biology & Department of Biochemistry, Pharmacy Building, Room 201, Temple University School of Medicine, Philadelphia, PA 19104, USA. noraengel@temple.edu.
Gene imprinting regulation involves complex processes. In the developing heart, Kcnq1 gene escapes silencing via novel chromatin loops, overriding non-coding RNA effects.
Area of Science:
- Developmental Biology
- Epigenetics
- Genomics
Background:
- Eukaryotic gene regulation involves transcriptionally silent and active chromatin domains.
- Imprinted domains exhibit parent-of-origin dependent monoallelic or biallelic expression.
- The Kcnq1 imprinted domain is regulated by the Kcnq1ot1 non-coding RNA.
Purpose of the Study:
- Investigate tissue-specific escape from imprinting of the Kcnq1 gene during development.
- Uncover the role of chromosome conformation in these regulatory events.
Main Methods:
- Chromosome conformation capture (3C) technology.
- Luciferase assays for in vitro regulatory element activity.
- Transgenic embryos for in vivo regulatory element activity.
Main Results:
- Kcnq1 transitions from monoallelic to biallelic expression in the developing heart during mid gestation.
- This transition occurs without Kcnq1 promoter demethylation.
- Tissue- and stage-specific chromatin loops form between the Kcnq1 promoter and novel regulatory elements.
Conclusions:
- Spatial organization of the Kcnq1 locus plays a crucial role in gene regulation.
- Novel mechanism identified where local gene activation overrides regional silencing by non-coding RNAs.
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