Matrix Attachment Region-Dependent Function of the Immunoglobulin μ Enhancer Involves Histone Acetylation at a Distance without Changes in Enhancer Occupancy

Nuclear matrix attachment regions (MARs), which flank the immunoglobulin μ heavy-chain enhancer on either side, are required for the activation of the distal variable-region (V(H)) promoter in transgenic mice. Previously, we have shown that the MARs extend a local domain of chromatin accessibility at the μ enhancer to more distal sites. In this report, we examine the influence of MARs on the formation of a nucleoprotein complex at the enhancer and on the acetylation of histones, which have both been implicated in contributing to chromatin accessibility. By in vivo footprint analysis of transgenic μ gene constructs, we show that the occupancy of factor-binding sites at the μ enhancer is similar in transcriptionally active wild-type and transcriptionally inactive ΔMAR genes. Chromatin immunoprecipitation experiments indicate, however, that the acetylation of histones at enhancer-distal nucleosomes is enhanced 10-fold in the presence of MARs, whereas the levels of histone acetylation at enhancer-proximal nucleosomes are similar for wild-type and ΔMAR genes. Taken together, these data indicate that the function of MARs in mediating long-range chromatin accessibility and transcriptional activation of the V(H) promoter involves the generation of an extended domain of histone acetylation, independent of changes in the occupancy of the μ enhancer.