DNase I sensitivity of immunoglobulin light chain genes in Abelson murine leukemia virus transformed pre-B cell lines

Persiani, Denise M.; Selsing, Erik

doi:10.1093/nar/17.13.5339

Cited by 15 publications

(6 citation statements)

References 26 publications

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“…Recombination at immunoglobulin and T-cell receptor loci is likely to be influenced by many factors, including transcription and accessibility (34)(35)(36)(37). The results presented in this paper introduce RSS as a previously underestimated factor affecting recombination frequency.…”

Section: Discussionmentioning

confidence: 79%

Mouse kappa light-chain recombination signal sequences mediate recombination more frequently than do those of lambda light chain.

Ramsden

1991

Proc. Natl. Acad. Sci. U.S.A.

110

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Immunoglobulin and T-cell receptor genes are somatically rearranged by site-specific recombination. Recombination signal sequences (RSS) have been identified as the major targeting element of this process. Recent reports demonstrate that differences in RSS affect the frequency of recombination, suggesting a role for RSS in the development of the B-cell repertoire. Examination of mouse light-chain RSS indicates that kappa light-chain RSS consistently show a greater degree of similarity to a consensus sequence than do those of lambda light chain. To determine whether this difference in natural RSS could affect the patterns of light-chain gene rearrangement and expression, we have constructed recombination substrates containing both a typical mouse kappa RSS pair and a typical mouse lambda RSS pair. Experiments using these substrates demonstrate that the kappa RSS pair mediates recombination at a vastly higher frequency than does the lambda RSS pair. This result argues that RSS differences may contribute significantly to the patterns of mouse immunoglobulin light-chain rearrangement, ultimately resulting in a high proportion of kappa light chain relative to lambda.

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Section: Discussionmentioning

confidence: 79%

Mouse kappa light-chain recombination signal sequences mediate recombination more frequently than do those of lambda light chain.

Ramsden

1991

Proc. Natl. Acad. Sci. U.S.A.

110

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“…The structure of the nucleosome was monitored by DNase I footprinting as a function of transcription and RecA-promoted DNA pairing (Fig. 6) (1,9,19,24). Experiments with transfected plasmid constructs suitable for recombination have also been performed, and the results suggested that the relationship between transcription and recombination in the V(D)J rearrangement events is only temporal (11).…”

Section: Resultsmentioning

confidence: 99%

Transcription activates RecA-promoted homologous pairing of nucleosomal DNA.

Kotani¹,

Kmiec²

1994

Mol. Cell. Biol.

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RecA protein catalyzes the homologous pairing of a single-stranded circular DNA and a linear duplex DNA molecule. When the duplex is packaged into chromatin, formation of homologously paired complexes is blocked. We have established a system for studying the RecA-promoted reaction by using a duplex fragment containing a single-phased nucleosome. Under these conditions there is no reaction leading to formation of joint molecule complexes. However, transcription on the chromatin template activates the formation of complexes. Reaction is dependent on RNA synthesis and DNA sequence homology and proceeds regardless of the direction of transcription.In general, chromatin is viewed as a repressive structure, down-regulating gene expression primarily by reducing the accessibility of trans-acting factors to their cognate binding sites (3,8,10,27). Repression extends to other processes such as genetic recombination, for which it has been observed in vitro that strand exchange promoted by Escherichia coli RecA protein is inhibited by chromatin (20). This raises the question of how recombination occurs in eukaryotes, in which genomes are packaged into chromatin. One notion that seems reasonable is that the homologous pairing and strand exchange machinery could gain access to DNA if chromatin structure were disrupted. DNA replication might be considered one means by which chromatin structure is disrupted. Here the helix is unwound and the relationship between the histones and DNA is altered (see reference 2 and references therein). Transcription is another process which, intuitively, would seem likely to destabilize or alter chromatin structure. Unwinding of the duplex resulting from binding by transcription factors or from active transcription might be supposed to disrupt chromatin structure sufficiently that recombination could be initiated.The activity of RNA polymerases on chromatin templates and the passage of RNA polymerase through nucleosomal particles has been the subject of intense investigation over the last several years. RNA polymerases from bacteriophages T7 and SP6 have been observed to transcribe through a nucleosome core assembled on a plasmid DNA sequence (13) or on a 5S RNA gene fragment (14). In similar in vitro studies with the eukaryotic enzyme RNA polymerase II or RNA polymerase III, transcriptional elongation was found to be inhibited by nucleosomes (16). The fate of the nucleosomes after polymerase transit through a nucleosome is a matter of controversy (4). In one well-studied case, nucleosomes were found to be completely displaced from a DNA template (13), whereas in another no net displacement was observed (14

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“…Increases in DNase I sensitivity and alterations in chromatin structure at the Ig locus have been reported to be associated with germline transcription and recombination (35)(36)(37)(38). We measured accessibility of the Ig locus to DNase I during induction of 103X7 cells by real-time PCR using primers for 13 amplicons spanning the Ig locus (Fig.…”

Section: Dnase I Accessibilitymentioning

confidence: 99%

Dynamic Changes in Accessibility, Nuclear Positioning, Recombination, and Transcription at the Igκ Locus

Fitzsimmons

Bernstein

Max

et al. 2007

The Journal of Immunology

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The 3-megabase Igκ locus undergoes differentially controlled nuclear positioning events and chromatin structural changes during the course of B cell development. The temporal association of chromatin structural changes, transcription, and recombination at the Igκ locus was determined in a murine pre-B cell line that can be induced to recombine at the Igκ locus and in ex vivo-cultured murine pre-B cells. Additionally, the timing of nuclear positioning relative to the temporal order of chromatin structural changes and recombination and transcription was determined. We demonstrate that before induction, the Igκ locus was poised for recombination; both alleles were in a contracted state, and the enrichment of histone modifications and germline transcripts of specific Vκ genes were observed. Histone modifications of the Vκ genes did not vary upon induction but the levels of modifications correlated with the levels of germline Vκ gene transcripts and recombination. Upon induction, but before VκJκ recombination, centromeric recruitment of single Igκ alleles occurred. DNase I sensitivity of the entire locus increased gradually over the course of differentiation while the enrichment of histone modifications downstream of the Vκ genes was increased in the silencer regions upstream of Jκ1, within the Igκ sterile transcript, the κ constant region, the Eκi and Eκ3′ enhancers, and the recombining sequence. The ex vivo pre-B cells showed similar patterns of histone modifications across the locus except at the Vκ genes. In this study, H3 acetylation correlated with levels of germline transcripts while H3 methylation correlated with levels of recombination.

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DNase I sensitivity of immunoglobulin light chain genes in Abelson murine leukemia virus transformed pre-B cell lines

Cited by 15 publications

References 26 publications

Mouse kappa light-chain recombination signal sequences mediate recombination more frequently than do those of lambda light chain.

Mouse kappa light-chain recombination signal sequences mediate recombination more frequently than do those of lambda light chain.

Transcription activates RecA-promoted homologous pairing of nucleosomal DNA.

Dynamic Changes in Accessibility, Nuclear Positioning, Recombination, and Transcription at the Igκ Locus

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