A poly(dA-dT) upstream activating sequence binds high-mobility group I protein and contributes to lymphotoxin (tumor necrosis factor-beta) gene regulation
| Autor: | R Reeves, S J Fashena, Nancy H. Ruddle |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1992 |
| Předmět: |
Lymphotoxin alpha
Regulation of gene expression Chloramphenicol O-Acetyltransferase Electrophoresis Base Sequence Molecular Sequence Data High Mobility Group Proteins Cell Biology Biology Regulatory Sequences Nucleic Acid Lymphotoxin beta Molecular biology Upstream activating sequence Lymphotoxin Gene Expression Regulation Poly dA-dT Regulatory sequence Gene expression Lymphotoxin beta receptor Molecular Biology Lymphotoxin-alpha Research Article Cell Line Transformed |
| Popis: | Lymphotoxin (LT; also known as tumor necrosis factor-beta) is a pleiotropic cytokine whose expression is tightly regulated in most cells and is repressed prior to activation signals. In some early B cells and Abelson murine leukemia virus-transformed pre-B-cell lines, LT mRNA is constitutively expressed. To examine the molecular regulation of the LT gene in a constitutively expressing cell line, we studied the Abelson murine leukemia virus-transformed lines PD and PD31. As demonstrated by primer extension analysis, constitutively expressed pre-B-cell-derived and inducibly expressed T-cell-derived LT mRNA were initiated at the same cap sites and predominant cap site utilization was conserved. Furthermore, we delineated an upstream activating sequence that was an important functional component of lymphotoxin transcriptional activation in PD and PD31 cells. The upstream activating sequence was localized to an essentially homopolymeric A + T-rich region (LT-612/-580), which was bound specifically by recombinant human high-mobility group I protein (HMG-I) and a PD/PD31 nuclear extract HMG-I (HMG-I-like) protein. The nuclear extract-derived HMG-I-like protein was recognized by anti-HMG-I antibody and bound to LT DNA to effect an electrophoretic mobility shift identical to that of bound recombinant human HMG-I. These findings implicate HMG-I in the regulation of constitutive lymphotoxin gene expression in PD and PD31 cells. HMG-I and HMG-I-like proteins could facilitate the formation of active initiation complexes by altering chromatin structure and/or by creating recognition sites for other activator DNA-binding proteins, some of which may be unique to or uniquely modified in these constitutive LT mRNA producers. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|