Transcription and Chromatin Analysis of Human Retroviruses
| dc.contributor.advisor | Kashanchi, Fatah | |
| dc.contributor.author | Akpamagbo, Yao A | |
| dc.creator | Akpamagbo, Yao A | |
| dc.date | 2016-08-26 | |
| dc.date.accessioned | 2017-10-03T17:28:10Z | |
| dc.date.available | 2017-10-03T17:28:10Z | |
| dc.description.abstract | During HIV infection, a provirus is integrated into the host genome where it is protected from transcription activators resulting in viral latency. Cellular long non-coding RNAs (lncRNA) and chromatin remodeling complexes (CRC) have recently emerged as key regulators in inhibitory pathways of infected cells. Here, we studied the activity of transcription inhibitors in HIV-infected cells to demonstrate that a novel HIV-1 RNA transcript, TAR-gag, is involved in HIV-1 latency. We also described a PBAF complex found only in HIV cells. Our results suggest that transcription inhibitors, CR8#13 and F07#13, independently regulate transcription machinery in infected cells via the pTEF-b complex. We also observed the presence of a BAF 170 complex only found in HIV-infected cells. The results indicate that a component of the pTEF-b complex, cdk9, phosphorylates both activator and inhibitor forms of BAF, and PBAF in the same cell. We then showed that TAR-gag is bound to the msin3A/HDAC CRC. Additionally, treatment of HIV-infected cells with F07#13 favored an interaction between TAR-gag, HDAC and PIWI proteins, whereas CR8#13 favored an interaction between TAR-gag, HDAC and mSin3A proteins. Given that TAR-gag is not translated and is increased by HIV transcription inhibitors in T-cells, the data suggest that it is a viral non-coding RNA that contributes to viral latency. | |
| dc.identifier | doi:10.13021/G8RD6V | |
| dc.identifier.uri | https://hdl.handle.net/1920/10750 | |
| dc.language.iso | en | |
| dc.title | Transcription and Chromatin Analysis of Human Retroviruses | |
| dc.type | Thesis | |
| thesis.degree.discipline | Biology | |
| thesis.degree.grantor | George Mason University | |
| thesis.degree.level | Master's | |
| thesis.degree.name | Master of Science in Biology |