Class switch recombination (CSR) involves a DNA rearrangement in the Ig heavy chain (IgH) gene that allows the same variable (V) region to be expressed with any one of the downstream constant region (C) genes to encode antibodies with many different effector functions. One hypothesis for how CSR is targeted to different C region genes is that histone modifications increase accessibility and/or recruit activation-induced cytosine deaminase (AID) and its associated processes to particular donor and recipient switch regions. In this work, we identified H3 acetyl K9 and H3 trimethyl K9 as histone modifications that correlate with the recombining pair of donor and recipient switch regions. The appearance of H3 trimethyl K9 is surprising because usually it is thought to mark silent genes and heterochromatin. Nevertheless, the time course of appearance of these histone modifications, the regions in IgH they associate with, and their appearance independent of AID damage suggest that both modifications play a role in targeting CSR.activation-induced cytoside deaminase ͉ B cells ͉ ChIP ͉ immunoglobulin A ntibodies are critical for the organism's defense against the many pathogens and toxins that it encounters. A diverse repertoire of antibodies is created by V(D)J rearrangement. Upon activation by their cognate antigen and T cells, B cells enter germinal centers where they express activation-induced cytosine deaminase (AID) that initiates somatic hypermutation (SHM) and class switch recombination (CSR) (1). SHM results in point mutations in the Ig heavy chain and light chain variable region genes, which code for the antigen-binding site, and with selection, these mutations lead to increased affinity for antigen (2). In CSR, the AID-induced mutations lead to double-stranded DNA breaks in the switch regions (SR) that are upstream of the antibody constant regions, and DNA rearrangements result in the apposition of different downstream constant region segments with the same heavy chain variable (V) region (3). Clonal progeny of an IgMexpressing B cell can express a particular V region with any one of the four IgG subclasses, IgE, or IgA. These isotypes have different effector functions and tissue localizations facilitating an effective response to a single antigenic determinant.The rearranged and productive IgH locus in mice and humans is organized in units consisting of a VDJ region, an intronic enhancer, followed by repeating units of intervening exons (I) and SRs that are noncoding, and the constant region (C) coding exons (Fig. 1A). Non-class-switched IgM-(IgD)-expressing B cells make the VDJ-C/C␦ transcript that is spliced and translated into a protein, and a sterile transcript that is not encoded into a protein and begins 5Ј of the I exon and continues through the SR and C regions.