External Seminar "Immunoglobulin Heavy Chain Enhancers as Regulator of B Lymphocyte Genome Architecture and Integrity" by Sandrine Le Noir

Title: Immunoglobulin Heavy Chain Enhancers as Regulator of B Lymphocyte Genome Architecture and Integrity

Speaker: Sandrine Le Noir

Affiliation: Université de Limoges

Abstract: During B-cell development, the immunoglobulin heavy chain locus (IgH) undergoes many genetic remodeling events including somatic hypermutation (SHM) and class switch recombination (CSR) which occurs in activated stages. These events imply DNA double strands breaks and thus require a tight regulation. This regulation is partly mediated by cis-regulatory elements distributed throughout the IgH locus, including the 3’ regulatory region (3’RR) and the MAR (Matrix attachement region) region. 

The 3’RR act as a super-enhancer containing four core elements (hs3a, hs1.2, hs3b and hs4) which are arranged in a quasi-palindrome structure centered on hs1.2. The MAR region is composed by a core enhancer (Eµ) and two Matrix attachment regions. While their roles in transcriptional control at the nucleosomal level are well-established, emerging evidence highlights the importance of nuclear dynamics in regulating B-cell development. Now, we investigate how IgH enhancers—specifically the 3’RR and matrix attachment regions (MARs)—shape nuclear and chromatin organization in resting and activated B cells. Using mouse models with total or partial deletions of 3’RR enhancers and MARs, we dissect their functional contributions to genomic organization and stability.