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Updated: Aug 8, 2025

Assessing Somatic Hypermutation in Ramos B Cells after Overexpression or Knockdown of Specific Genes
Published on: November 1, 2011
The IgH Eµ-MAR regions promote UNG-dependent error-prone repair to optimize somatic hypermutation
Ophélie A Martin1, Morgane Thomas1, Marie Marquet1
1Laboratoire Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges, CNRS Unité Mixte de Recherche 7276, Inserm Unité 1262, Limoges, France.
Intoduction:
Two scaffold/matrix attachment regions (5'- and 3'-MARs ) flank the intronic core enhancer (cEµ) within the immunoglobulin heavy chain locus (IgH). Besides their conservation in mice and humans, the physiological role of MARs is still unclear and their involvement in somatic hypermutation (SHM) has never been deeply evaluated.
Methods:
Our study analyzed SHM and its transcriptional control in a mouse model devoid of MARs , further combined to relevant models deficient for base excision repair and mismatch repair.
Results:
We observed an inverted substitution pattern in of MARs -deficient animals: SHM being decreased upstream from cEµ and increased downstream of it. Strikingly, the SHM defect induced by MARs -deletion was accompanied by an increase of sense transcription of the IgH V region, excluding a direct transcription-coupled effect. Interestingly, by breeding to DNA repair-deficient backgrounds, we showed that the SHM defect, observed upstream from cEµ in this model, was not due to a decrease in AID deamination but rather the consequence of a defect in base excision repair-associated unfaithful repair process.
Discussion:
Our study pointed out an unexpected "fence" function of MARs regions in limiting the error-prone repair machinery to the variable region of Ig gene loci.
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