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Heterochromatin Effects on the Frequency and Duration of LCR-Mediated Gene Transcription
Open accessAbstract
Locus control regions (LCRs) are responsible for initiating and maintaining a stable tissue-specific open chromatin structure of a locus. In transgenic mice, LCRs confer high level expression on linked genes independent of position in the mouse genome. Here we show that an incomplete LCR loses this property when integrated into heterochromatic regions. Two disruption mechanisms were observed. One is classical position-effect variegation, resulting in continuous transcription in a clonal subpopulation of cells. The other is a novel mechanism resulting in intermittent gene transcription in all cells. We conclude that only a complete LCR fully overcomes heterochromatin silencing and that it controls the level of transcription by ensuring activity in all cells at all times rather than directly controlling the rate of transcription.
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“deletion of HS1 from the SE results in substantial sensitivity to position effects in transgenic mice;46”
From Super-enhancers include classical enhancers and facilitators to fully activate gene expression (2023) · cites this paper as [46]
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Metadata
- Authors
- Milot, E., Strouboulis, J., Trimborn, T., Wijgerde, M., de Boer, E., Langeveld, A., Tan-Un, K., Vergeer, W., Yannoutsos, N., Grosveld, F., & Fraser, P.
- Affiliations
- National Institute for Medical Research (GB)
- Erasmus MC (NL)
- Corresponding author
- Grosveld, Frank
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1996-10
- Volume
- 87
- Issue
- 1
- Pages
- 105-114
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2151390187
- Cited by
- 314
- References
- 42
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 2 · 2021: 1 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 3 · 2014: 2 · 2013: 6 · 2012: 8
- FWCI
- 13.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- locus control region, heterochromatin, position effect variegation, gene transcription, transcriptional silencing, tissue-specific gene expression, open chromatin, transgenic mice
- MeSH terms
- Animals, Centromere, Chromosome Mapping, Deoxyribonuclease I, Erythrocytes, Gene Expression Regulation, Globins, Heterochromatin, Humans, Mice, Transgenic, Regulatory Sequences, Nucleic Acid, RNA, Messenger, Time Factors, Transcription, Genetic, Deoxyribonucleases, Type II Site-Specific, Single-Strand Specific DNA and RNA Endonucleases, Sequence Deletion, Gene Dosage, Transgenes, Mice
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