Cell Lineage Specificity of Chromatin Configuration Around the Immunoglobulin Heavy Chain Enhancer

As tested by DNase I hypersensitivity, the chromatin structure of the IgH enhancer region in human B cell precursor cell lines is in an open or accessible conformation. All T cell lines, with either germline or rearranged IgH genes, were also hypersensitive to DNase I but in contrast to B cell precursors showed no detectable Cmu expression. Normal thymocytes similarly had a hypersensitive IgH enhancer site. In contrast to lymphoid cells, all myeloid cell lines tested, as well as normal granulocytes, were not DNase I hypersensitive and did not express Cmu. A putative lymphomyeloid progenitor cell line KG1, although having a germline configuration of Ig genes, produced Cmu transcripts and was hypersensitive to DNase I in the IgH enhancer region. After induction of myeloid differentiation the Ig enhancer region of KG1 cells is no longer hypersensitive or transcriptionally active. Two HhaI restriction sites on either side of the IgH enhancer were not methylated in all Cmu-expressing lines but methylated in non-expressing cell lines. These results show that an open chromatin structure around the heavy chain enhancer is necessary but insufficient for initiating transcription from unrearranged IgH genes and further suggests this region may be in an open or accessible configuration prior to lineage commitment and closed following adoption of the myeloid lineage.