Regulation of Germline Promoters by the Two Human Ig Heavy Chain 3′ α Enhancers
| Autor: | Qiang Pan, Yanzhong Hu, Lennart Hammarström, Ralph M. Bernstein, Evangelia Pardali, Frederick C. Mills, Paschalis Sideras, Edward E. Max |
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| Rok vydání: | 2000 |
| Předmět: |
Immunology
Enhancer RNAs Biology Immunoglobulin alpha-Chains Jurkat cells Adjuvants Immunologic Transforming Growth Factor beta Transcription (biology) Tumor Cells Cultured Humans Immunology and Allergy Promoter Regions Genetic Enhancer 3' Untranslated Regions Gene Locus control region Promoter Locus Control Region Immunoglobulin Class Switching Molecular biology Enhancer Elements Genetic Germ Cells Gene Expression Regulation Cell culture Immunoglobulin Constant Regions Immunoglobulin Heavy Chains |
| Zdroj: | The Journal of Immunology. 164:6380-6386 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.164.12.6380 |
| Popis: | The human IgH 3′ enhancers, located downstream of each of the two Cα genes, modulate germline (GL) transcription of the IgH genes by influencing the activity of promoter-enhancer complexes upstream of the switch and intervening (I) regions. The regulation of GL α1 and α2 promoters by different human 3′ enhancer fragments was investigated in cell lines representing various developmental stages. Both α1HS1,2 and α2HS1,2 fragments show equally strong enhancer activity on the GL α1 and α2 promoters in both orientations when transiently transfected into a number of mature B cell line (DG75, CL-01, and HS Sultan). However, there is no activity in a human pre-B cell line (NALM-6) nor a human T cell line (Jurkat). HS3 shows no enhancer activity by itself in any of the cell lines, whereas a modest effect is noted using HS4 in the three mature B cell lines. However, the combination of the α2HS3-HS1,2-HS4 fragments, which together form a potential locus control region, displays a markedly stronger enhancer activity than the individual fragments with a differential effect on the α1 and α2 promoters as compared with the γ3 promoter. Our results suggest that the human GL α promoter may be regulated by two independent pathways. One pathway is induced by TGF-β1 which directs IgA isotype switch through activation of the GL α promoter and no TGF-β1-responsive elements are present in the different 3′ enhancer fragments. The other route is through the human 3′ enhancer regions that cis-up-regulate the GL α promoter activity in mature B cells. |
| Databáze: | OpenAIRE |
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