ArticleMolecular and cellular biology1999
Variegated expression of the endogenous immunoglobulin heavy-chain gene in the absence of the intronic locus control region.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- The IgHFrontiers in immunology · 2023Article
- Article
- In search of lost time: Enhancers as modulators of timing in lymphocyte development and differentiation.Immunological reviews · 2021Review
- Identification of a novel cis-regulatory element essential for immune tolerance.The Journal of experimental medicine · 2015Article
- Memories of lost enhancers.Genes & development · 2010Article
- Enhancers: the abundance and function of regulatory sequences beyond promoters.Developmental biology · 2010Review
- Functional characterization of a tobacco matrix attachment region-mediated enhancement of transgene expression.Transgenic research · 2009Article
- Position effect variegation and imprinting of transgenes in lymphocytes.Nucleic acids research · 2008Article
- Article
- Forced expression of AID facilitates the isolation of class switch variants from hybridoma cells.Journal of immunological methods · 2006Article
- Slow, stochastic transgene repression with properties of a timer.Genome biology · 2006Article
- A system for precise analysis of transcription-regulating elements of immunoglobulin genes.BMC biotechnology · 2005Article
- Complex regulation of somatic hypermutation by cis-acting sequences in the endogenous IgH gene in hybridoma cells.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- TM2, a novel strong matrix attachment region isolated from tobacco, increases transgene expression in transgenic rice calli and plants.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2005Article
- Article
- Lentivirus vectors incorporating the immunoglobulin heavy chain enhancer and matrix attachment regions provide position-independent expression in B lymphocytes.Journal of virology · 2003Article
- Elevation of transgene expression level by flanking matrix attachment regions (MAR) is promoter dependent: a study of the interactions of six promoters with the RB7 3' MAR.Transgenic research · 2003Article
- The murine beta-globin locus control region regulates the rate of transcription but not the hyperacetylation of histones at the active genes.Proceedings of the National Academy of Sciences of the United States of America · 2001Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression of chromosomally integrated transgenes usually varies greatly among independent transfectants. This variability in transgene expression has led to the definition of locus control regions (LCRs) as elements which render expression consistent. Analyses of expression in single cells revealed that the expression of transgenes which lack an LCR is often variegated, i.e., on in some cells and off in others. In many cases, transgenes which show variegated expression were found to have inserted near the centromere. These observations have suggested that the LCR prevents variegation by blocking the inhibitory effect of heterochromatin and other repetitive-DNA-containing structures at the insertion site and have raised the question of whether the LCR plays a similar role in endogenous genes. To address this question, we have examined the effects of deleting the LCR from the immunoglobulin heavy-chain locus of a mouse hybridoma cell line in which expression of the immunoglobulin mu heavy-chain gene is normally highly stable. Our analysis of mu expression in single cells shows that deletion of this LCR resulted in variegated expression of the mu gene. That is, in the absence of the LCR, expression of the mu gene in the recombinant locus could be found in either of two epigenetically maintained, metastable states, in which transcription occurred either at the normal rate or not at all. In the absence of the LCR, the on state had a half-life of approximately 100 cell divisions, while the half-life of the off state was approximately 40,000 cell divisions. For recombinants with an intact LCR, the half-life of the on state exceeded 50,000 cell divisions. Our results thus indicate that the LCR increased the stability of the on state by at least 500-fold.
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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.