DNA regions flanking the mouse Ig 3'α enhancer are differentially methylated and DNAse I hypersensitive during B cell differentiation

Two B cell-specific enhancer elements are associated with the IgH gene cluster. One enhancer is located within the I-Cμ intron (Eμ), whereas a second enhancer (3'αE) is approximately 12.5 kb 3' of the Cα membrane exon. In an attempt to understand the function of 3'αE, we have characterized its surrounding structural milieu during various stages of B cell differentiation through analysis of methylation patterns and the identification of DNAse I- hypersensitive sites. We observed a correlation between the chromatin structure of this region and the differentiation state of the cell. Compared to liver and brain, the region 3' of α was hypermethylated in pre-B and T cell lines and became progressively demethylated as B cell differentiation continued. A DNAse I-hypersensitive site was present in pre-B cell lines about 17 kb 3' of 3'αE. In fully differentiated myeloma cell lines, a second cluster of DNAse I-hypersensitive sites was present immediately 5' of 3'αE. Our data indicate that the 3'α enhancer is relatively sequestered during early stages of B cell differentiation and becomes increasingly accessible at later stages.