A stage-specific enhancer of immunoglobulin J chain gene is induced by interleukin-2 in a presecretor B cell stage.
Interleukin-2 (IL-2)-induced transcription of the J chain gene was used as a model for analyzing cytokine regulation during B cell development. To determine whether IL-2 signals are targeted to a J chain gene enhancer as well as to its promoter, the sequences flanking the J chain gene were first examined for DNase I hypersensitivity. Of six sites identified, two strong ones, 7.5 kb upstream of the J chain gene, were found to be associated with an enhancer that is active only during the antigen-driven stages of B cell development. Further analyses of the enhancer in the IL-2-responsive presecretor BCL1 cells showed that the enhancer is activated at this stage by an IL-2 signal that functions by opening the enhancer chromatin and stimulating STAT5 to bind to a STAT5 element critical for the enhancer induction. Moreover, after this early induction stage, the enhancer was shown to be constitutively open and active in terminally differentiated plasma cells.
Kang
C J
CJ
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA. chjkang@plaza1.snu.ac.kr
Sheridan
C
C
Koshland
M E
ME
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D017930:Genes, Reporter; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D007144:Immunoglobulin J-Chains / Q000235:genetics*; D007376:Interleukin-2 / Q000494:pharmacology*; D008894:Milk Proteins; D018448:Models, Immunological; D008969:Molecular Sequence Data; D010950:Plasma Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D011401:Promoter Regions, Genetic; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D007144:Immunoglobulin J-Chains; D007376:Interleukin-2; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D003850:Deoxyribonuclease I