AID-dependent histone acetylation is detected in immunoglobulin S regions

Class switch recombination (CSR) is regulated by the expression of activation-induced deaminase ( AID) and germline transcripts (GLTs). AID-dependent double-strand breaks (DSBs) are introduced into switch ( S) regions and stimulate CSR. Although histone acetylation (Ac) has been well documented in transcription regulation, its role in DNA damage repair remains largely unexplored. The 1B4.B6 B cell line and normal splenic B cells were activated to undergo CSR and analyzed for histone Ac by chromatin immunoprecipitation (ChIP). A detailed study of the I gamma 3-S gamma 3-C gamma 3 locus demonstrated that acetylated histones are focused to the I gamma 3 exon and the S gamma 3 region but not to the intergenic areas. Histone H3 Ac is strongly correlated with GLT expression at four S regions, whereas H4 Ac was better associated with B cell activation and AID expression. To more directly examine the relationship between H4 Ac and AID, LPS-activated AID KO and WT B cells were analyzed and express comparable levels of GLTs. In AID-deficient B cells, both histones H3 and H4 are reduced where H4 is more severely affected as compared with WT cells. Our findings raise the intriguing possibility that histone H4 Ac at S regions is a marker for chromatin modifications associated with DSB repair during CSR.