The IgH Eµ-MAR regions promote UNG-dependent error-prone repair to optimize somatic hypermutation.

ABSTRACT:

Intoduction

Two scaffold/matrix attachment regions (5'- and 3'-MARs_Eµ ) 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_Eµ 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_Eµ , further combined to relevant models deficient for base excision repair and mismatch repair.

Results

We observed an inverted substitution pattern in of MARs_Eµ -deficient animals: SHM being decreased upstream from cEµ and increased downstream

SUBMITTER: Martin OA 

PROVIDER: S-EPMC9971809 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature