A Negative Regulatory Element in the bcl-2 5'-Untranslated Region Inhibits Expression from an Upstream Promoter
| Autor: | Young, R L, Korsmeyer, S J |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Cell Nucleus
B-Lymphocytes Base Sequence Transcription Genetic Molecular Sequence Data Restriction Mapping Cytomegalovirus Templates Genetic Cell Biology Regulatory Sequences Nucleic Acid Transfection Cell Line Open Reading Frames Gene Expression Regulation Proto-Oncogene Proteins c-bcl-2 Mutagenesis Protein Biosynthesis Proto-Oncogene Proteins Proto-Oncogenes Humans Promoter Regions Genetic Molecular Biology Research Article Plasmids Sequence Deletion |
| Zdroj: | Molecular and Cellular Biology. 13:3686-3697 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.13.6.3686-3697.1993 |
| Popis: | bcl-2 mRNA is present at high levels in pre-B-cell lines but is down-regulated in most mature B-cell lines. To investigate the mechanisms responsible for its developmental control, we studied the regulation of bcl-2 expression in human B-lineage cell lines. Using nuclear run-on assays, we found that bcl-2 transcription decreases in parallel with levels of steady-state mRNA during B-cell development. To define cis-acting elements that regulate bcl-2 transcription, we analyzed the expression of transiently transfected promoter-reporter constructs. We identified a novel negative regulatory element (NRE) in the bcl-2 5'-untranslated region that decreased expression from the bcl-2 P1 promoter or heterologous promoters in a position-dependent fashion. The NRE functions in either orientation but contains distinct orientation-dependent subfragments. Additional analyses demonstrated that multiple, functionally redundant sequence elements mediate NRE activity. Though the bcl-2 NRE is active in pre-B- and mature B-cell lines, chromatin structure of the endogenous NRE differs in these cells, suggesting that its activity or effect may vary during B-cell development. Our results indicate that negative control of transcription initiated at the P1 promoter is an important determinant of the differential expression of bcl-2. |
| Databáze: | OpenAIRE |
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