DNA regions flanking the mouse Ig 3' alpha enhancer are differentially methylated and DNAase 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 J-C mu intron (E mu), whereas a second enhancer (3' alpha E) is approximately 12.5 kb 3' of the C alpha membrane exon. In an attempt to understand the function of 3' alpha E, 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 alpha 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' alpha E. In fully differentiated myeloma cell lines, a second cluster of DNAse I-hypersensitive sites was present immediately 5' of 3' alpha E. Our data indicate that the 3' alpha enhancer is relatively sequestered during early stages of B cell differentiation and becomes increasingly accessible at later stages.
Giannini
S L
SL
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461.
Singh
M
M
Calvo
C F
CF
Ding
G
G
Birshtein
B K
BK
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000494:pharmacology*; D004742:Enhancer Elements, Genetic; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008745:Methylation; D051379:Mice; D008815:Mice, Inbred Strains; D009693:Nucleic Acid Hybridization
D007143:Immunoglobulin Heavy Chains; D004247:DNA; D003850:Deoxyribonuclease I