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Publication : Deciphering the importance of the palindromic architecture of the immunoglobulin heavy-chain 3' regulatory region.

First Author  Saintamand A Year  2016
Journal  Nat Commun Volume  7
Pages  10730 PubMed ID  26883548
Mgi Jnum  J:234741 Mgi Id  MGI:5790763
Doi  10.1038/ncomms10730 Citation  Saintamand A, et al. (2016) Deciphering the importance of the palindromic architecture of the immunoglobulin heavy-chain 3' regulatory region. Nat Commun 7:10730
abstractText  The IgH 3' regulatory region (3'RR) controls class switch recombination (CSR) and somatic hypermutation (SHM) in B cells. The mouse 3'RR contains four enhancer elements with hs1,2 flanked by inverted repeated sequences and the centre of a 25-kb palindrome bounded by two hs3 enhancer inverted copies (hs3a and hs3b). hs4 lies downstream of the palindrome. In mammals, evolution maintained this unique palindromic arrangement, suggesting that it is functionally significant. Here we report that deconstructing the palindromic IgH 3'RR strongly affects its function even when enhancers are preserved. CSR and IgH transcription appear to be poorly dependent on the 3'RR architecture and it is more or less preserved, provided 3'RR enhancers are present. By contrast, a 'palindromic effect' significantly lowers VH germline transcription, AID recruitment and SHM. In conclusion, this work indicates that the IgH 3'RR does not simply pile up enhancer units but also optimally exposes them into a functional architecture of crucial importance.
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