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Stimulation of Tat-associated kinase-independent transcriptional elongation from the human immunodeficiency virus type-1 long terminal repeat by a cellular enhancer.
| Content Provider | Semantic Scholar |
|---|---|
| Author | West, Michelle J. Karn, Jonathan |
| Copyright Year | 1999 |
| Abstract | The human immunodeficiency virus type-1 (HIV-1) long terminal repeat (LTR) initiates transcription efficiently but produces only short transcripts in the absence of the trans-activator protein, Tat. To determine whether a cellular enhancer could provide the signals required to recruit an elongation-competent polymerase to the HIV-1 LTR, the B cell-specific immunoglobulin heavy chain gene enhancer (IgHE) was inserted upstream of the LTR. The enhancer increased transcription in the absence of Tat between 6- and 7-fold in transfected B cells, but the full-length transcripts remained at basal levels in HeLa cells, where the enhancer is inactive. RNase-protection studies showed that initiation levels in the presence and absence of the enhancer were constant, but the enhancer significantly increased the elongation capacity of the polymerases. Tat-stimulated elongation is strongly inhibited by the nucleoside analogue 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), which inhibits the Tat-associated kinase, TAK (CDK9). However, polymerases initiating transcription from LTRs carrying the enhancer were able to efficiently elongate in the presence of DRB. Specific repression of TAK by expression in trans of the CDK9 kinase also inhibited Tat-stimulated elongation but did not inhibit enhancer-dependent transcription significantly. Thus, the activation of polymerase processivity by the IgHE involves a unique mechanism which is independent of TAK. |
| Starting Page | 3085 |
| Ending Page | 3088 |
| Page Count | 4 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://emboj.embopress.org/content/embojnl/18/5/1378.full.pdf |
| PubMed reference number | 10064603v1 |
| Volume Number | 18 |
| Issue Number | 5 |
| Journal | The EMBO journal |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Analog CDK9 gene CDK9 protein, human CDK9 wt Allele DSIF complex Daunorubicin Dichlororibofuranosylbenzimidazole Enhancer of transcription HIV IGH gene Immunoglobulin Heavy Chains Immunologic Deficiency Syndromes Inactive - Biochemical Activity Level Leukemia, B-Cell Long Terminal Repeat Nucleoside Analogs Nucleosides Repression, Psychology SLC3A2 gene Terminal Repeat Sequences Trans-Activators Transcript Transcription Elongation, Genetic Transcription Initiation Transcription, Genetic |
| Content Type | Text |
| Resource Type | Article |
