Replacement of Iμ-Cμ intron by NeoR gene alters Iμ germ-line expression but has no effect on V(D)J recombination

Haddad, Dania; Dougier, Hei-Lanne; Laviolette, Nathalie; Puget, Nadine; Khamlichi, Ahmed Amine

doi:10.1016/j.molimm.2009.11.024

Cited by 3 publications

(5 citation statements)

References 52 publications

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“…Both strands are similarly targeted by AID: Mice deficient for DNA-repair proteins UNG and Msh2 revealed no marked preference for targeting of the transcribed versus non-transcribed strand [50]. Anti-sense transcription across the IgH locus has been proposed to facilitate the interaction of AID with the template strand [80] but was not found to be essential for CSR [40, 81]. Intriguing, recent findings indicate that the RNA exosome complex is involved.…”

Section: Aid Targetingmentioning

confidence: 99%

AID targeting: old mysteries and new challenges

Chandra

Bortnick

Murre

2015

Trends in Immunology

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Activation-induced cytidine deaminase (AID) mediates cytosine deamination and underlies two central processes in antibody diversification: somatic hypermutation and class-switch recombination. AID deamination is not exclusive to immunoglobulin loci; it can instigate DNA lesions in non-immunoglobulin genes and thus, stringent checks are in place to constrain and restrict its activity. Recent findings have provided new insights into the mechanisms that target AID activity to specific genomic regions, revealing an involvement for non-coding RNAs associated with polymerase pausing and with enhancer transcription as well as genomic architecture. We review these findings and integrate them into a model for multi-level regulation of AID expression and targeting in immunoglobulin and non-immunoglobulin loci. Within this framework we discuss gaps in understanding, and outline important areas of further research.

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Section: Aid Targetingmentioning

confidence: 99%

AID targeting: old mysteries and new challenges

Chandra

Bortnick

Murre

2015

Trends in Immunology

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“…B cells from bone marrow were sorted by using CD19‐magnetic microbeads and LS columns (Miltenyi Biotec) and total RNA was reverse transcribed (Invitrogen) and subjected to PCR. Quantification was as described (Haddad et al , 2010).…”

Section: Methodsmentioning

confidence: 99%

“…For GL transcription, the primers, the RT–PCR conditions and the expected sizes of the PCR products have been described (Oruc et al , 2007; Haddad et al , 2010). pA1, GATGGAGAGCGTATGTTAGTAC.…”

Section: Methodsmentioning

confidence: 99%

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Sense transcription through the S region is essential for immunoglobulin class switch recombination

et al. 2011

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Class switch recombination (CSR) occurs between highly repetitive sequences called switch (S) regions and is initiated by activation-induced cytidine deaminase (AID). CSR is preceded by a bidirectional transcription of S regions but the relative importance of sense and antisense transcription for CSR in vivo is unknown. We generated three mouse lines in which we attempted a premature termination of transcriptional elongation by inserting bidirectional transcription terminators upstream of Sμ, upstream of Sγ3 or downstream of Sγ3 sequences. The data show, at least for Sγ3, that sense transcriptional elongation across S region is absolutely required for CSR whereas its antisense counterpart is largely dispensable, strongly suggesting that sense transcription is sufficient for AID targeting to both DNA strands.

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“…Several models have been put forward to account for deamination of template strand. Anti-sense transcription through the IgH locus has been proposed to facilitate access of AID to the template strand (75); however, anti-sense transcription is not essential for CSR (76). Components of the RNA exosome complex have been shown to interact with AID and mediate accessibility to the template strand by degrading the nascent RNA hybridized to the template strand (77).…”

Section: Accessibility and Targeting Of Aidmentioning

confidence: 99%

AIDing Chromatin and Transcription-Coupled Orchestration of Immunoglobulin Class-Switch Recombination

et al. 2014

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Secondary diversification of the antibody repertoire upon antigenic challenge, in the form of immunoglobulin heavy chain (IgH) class-switch recombination (CSR) endows mature, naïve B cells in peripheral lymphoid organs with a limitless ability to mount an optimal humoral immune response, thus expediting pathogen elimination. CSR replaces the default constant (CH) region exons (Cμ) of IgH with any of the downstream CH exons (Cγ, Cε, or Cα), thereby altering effector functions of the antibody molecule. This process depends on, and is orchestrated by, activation-induced deaminase (AID), a DNA cytidine deaminase that acts on single-stranded DNA exposed during transcription of switch (S) region sequences at the IgH locus. DNA lesions thus generated are processed by components of several general DNA repair pathways to drive CSR. Given that AID can instigate DNA lesions and genomic instability, stringent checks are imposed that constrain and restrict its mutagenic potential. In this review, we will discuss how AID expression and substrate specificity and activity is rigorously enforced at the transcriptional, post-transcriptional, post-translational, and epigenetic levels, and how the DNA-damage response is choreographed with precision to permit targeted activity while limiting bystander catastrophe.

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Replacement of Iμ-Cμ intron by NeoR gene alters Iμ germ-line expression but has no effect on V(D)J recombination

Cited by 3 publications

References 52 publications

AID targeting: old mysteries and new challenges

AID targeting: old mysteries and new challenges

Sense transcription through the S region is essential for immunoglobulin class switch recombination

AIDing Chromatin and Transcription-Coupled Orchestration of Immunoglobulin Class-Switch Recombination

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