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 Igamma3-Sgamma3-Cgamma3 locus demonstrated that acetylated histones are focused to the Igamma3 exon and the Sgamma3 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.
Wang
Lili
L
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
Whang
Naree
N
Wuerffel
Robert
R
Kenter
Amy L
AL
D000107:Acetylation; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002843:Chromatin / Q000276:immunology / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006657:Histones / Q000276:immunology / Q000378:metabolism*; D017578:Immunoglobulin Class Switching; D007134:Immunoglobulin Switch Region; D008070:Lipopolysaccharides; D051379:Mice; D018345:Mice, Knockout; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D002843:Chromatin; D006657:Histones; D008070:Lipopolysaccharides; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase