The IgH 3 regulatory region (3RR) controls class switch recombination (CSR) and somatic hypermutation (SHM) in B cells. The mouse 3RR contains four enhancer elements with hs1,2 flanked by inverted repeated sequences and the center of a 25-kb palindrome bounded by two hs3 enhancer inverted copies (hs3a and hs3b). hs4 lies downstream of the palindrome. Evolution maintained in mammals this unique palindromic arrangement suggesting that it is functionally significant. We report that deconstructing the palindromic IgH 3RR strongly impacts its function even when enhancers are preserved. CSR and IgH transcription appear poorly dependent from the 3RR architecture and are more or less preserved provided 3RR enhancers are present. By contrast, an architectural effect significantly lowers VH germline transcription, AID recruitment and SHM. In conclusion, this work indicates that the IgH 3RR does not simply pile up enhancer units but also optimally expose them into a functional architecture of crucial importance. SOURCE: Kevin LebrigandFunctional Genomics Platform of Nice-Sophia-Antipolis, France. IPMC/CNRS

Pluto Bioinformatics

GSE76359: Deciphering the importance of the palindromic architecture of the immunoglobulin heavy chain 3 regulatory region.