Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting

@article{Gu1993IndependentCO,
  title={Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting},
  author={Hua Gu and Yong-Rui Zou and Klaus Rajewsky},
  journal={Cell},
  year={1993},
  volume={73},
  pages={1155-1164}
}
Immunoglobulin class-switch recombination in mice devoid of any S mu tandem repeat.
TLDR
It is proposed that the core E mu enhancer plays a central role in the temporal dissociation of somatic hypermutation from class switching, and could be the boundary for CSR-associated somatic mutations.
An extrachromosomal switch recombination substrate reveals kinetics and substrate requirements of switch recombination in primary murine B cells.
TLDR
A novel type of switch recombination substrate is tested, constructed according to the intron-exon structure of the IgH locus, but with heterologous elements, to test the structural requirements for targeting and the kinetics ofswitch recombination in activated primary murine B cells.
A site–directed chromosomal translocation induced in embryonic stem cells by Cre-loxP recombination
TLDR
A strategy for chromosome engineering in embryonic stem (ES) cells that relies on sequential gene targeting and Cre–loxP site–specific recombination and will allow the design of a variety of chromosome rearrangements that can be selected and verified in ES cells or activated in ES cell–derived mice.
A genetic screen identifies novel non-compatible loxP sites.
TLDR
A genetic screen designed to identify novel mutant spacer-containing lox sites displaying enhanced incompatibility with the canonical loxP site is carried out, and one of the mutant sites recovered appears to be completely stable in HEK293 cells and supports recombinase-mediated cassette exchange in bacteria and mammalian cell culture.
Transcription targets recombination at immunoglobulin switch sequences in a strand-specific manner.
TLDR
Immunoglobulin (lg) heavy chain gene assembly can be divided into two developmentally and mechanistically distinct phases during B cell maturation, and by changing antibody class, or isotype, the same antigen specificity can be associated with a variety of effector functions.
Accessibility Control of Recombination at Immunoglobulin Locus
TLDR
This review focuses on the control of CSR by modulation of accessibility, and the role of histone modifications and germline transcription in CSR.
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TLDR
Recombination to a particular switch region was abolished in mice that were altered to lack sequences that are 5' to the s gamma 1 region, which directly implicates the functional importance of 5' switch region flanking sequences in the control of class switch recombination.
Transcriptional regulatory elements stimulate recombination in extrachromosomal substrates carrying immunoglobulin switch-region sequences.
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TLDR
A sensitive genetic assay is developed to analyze DNA sequences and regulatory elements required for immunoglobulin heavy chain isotype switch recombination in substrates containing mu and gamma 3 chain switch (S)-region sequences.
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TLDR
It is demonstrated that a procaryotic recombinase can enter a eucaryotic nucleus and, moreover, that the ability of the Cre recomb inase to perform precise recombination events on the chromosomes of S. cerevisiae is unimpaired by chromatin structure.
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TLDR
Interleukin 4 may play a critical role in programming murine B‐lymphocytes for specific switch recombination and rearrangement from active and inactive IgH loci of B‐cells activated in various ways and immortalized by cell fusion.
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TLDR
Tumor formation resulted from large tumor-antigen activation via site-specific, Cre-mediated deletion of Stop sequences, and was confirmed through analysis of double-transgenic offspring developed lens tumors.
Complete nucleotide sequence of the murine gamma 3 switch region and analysis of switch recombination sites in two gamma 3-expressing hybridomas.
TLDR
This work studied switches to the gamma 3 isotype by sequencing the entire gamma 3 switch region and molecularly cloned rearranged switch regions from two gamma 3-expressing hybridomas and determined the DNA sequences at the mu-gamma 3 recombination sites.
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TLDR
It is reported that transcription of a supercoiled plasmid containing the murine IgA switch region (Sα) leads to a loss of superhelical turns and the resulting series of less supercoiling plasmids is stabilized by RNA-DNA hybrids formed by the nascent RNA transcripts, which remain base-paired with their DNA templates.
Switch region content of hybridomas: the two spleen cell Igh loci tend to rearrange to the same isotype.
TLDR
These experiments suggest that the heavy chain switch rearrangement in normal spleen cells is a deletion event that occurs within tandemly repeated elements and is mediated by factors with partial, or perhaps complete, isotype specificity.
Targeted insertion of exogenous DNA into the eukaryotic genome by the Cre recombinase.
TLDR
It is shown that intermolecular Cre-mediated recombination can specifically direct the integration of a loxP-containing circular DNA into a chromosomal lox P site, both in yeast and in mammalian cells.
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