Somatic hypermutation (SHM) diversifies the V region of Ig genes and underlies 
the process of affinity maturation, in which B lymphocytes producing 
high-affinity Abs are generated and selected. SHM is triggered in activated B 
cells by deamination of deoxycytosine residues mediated by activation-induced 
deaminase (AID). Whereas mistargeting of SHM and AID results in mutations and 
DNA damage in many non-Ig genes, they act preferentially at Ig loci. The 
mechanisms responsible for preferential targeting of SHM and AID activity to Ig 
loci are poorly understood. Using an assay involving an SHM reporter cassette 
inserted into the Ig L chain locus (IgL) of chicken DT40 B cells, we have 
identified a 1.9-kb DIVAC (diversification activator) element derived from 
chicken IgL that supports high levels of AID-dependent mutation activity. 
Systematic deletion analysis reveals that targeting activity is spread 
throughout much of the sequence and identifies two core regions that are 
particularly critical for function: a 200-bp region within the IgL enhancer, and 
a 350-bp 3' element. Chromatin immunoprecipitation experiments demonstrate that 
whereas DIVAC does not alter levels of several epigenetic marks in the mutation 
cassette, it does increase levels of serine-5 phosphorylated RNA polymerase II 
in the mutation target region, consistent with an effect on transcriptional 
elongation/pausing. We propose that multiple, dispersed DNA elements collaborate 
to recruit and activate the mutational machinery at Ig gene variable regions 
during SHM.