Alur P, Laughlin M; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 3rd Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 3rd 1996 Wash D C. 1996 Jan 28-Feb 1; 3rd: 63.
The Dorrance H. Hamilton Laboratories, Thomas Jefferson University, Philadelphia, PA.
A key feature of the life cycle of HIV-1 is integration into the host cell's genome. Once integration takes place, it might be expected that the cell can modulate this small proviral gene cluster much as it does the vast number of other gene clusters within its genome. The eukaryotic genome is organized into compact (and complex) secondary and tertiary structures to allow for the efficient packaging of DNA into chromatin. On a macroscopic scale, one of the functional units of chromatin is the chromatin domain whose 5' and 3' boundaries are anchored to the nuclear matrix by unique DNA sequences termed matrix attachment regions (MARs). Within these boundaries are a single gene or small cluster of related genes with their regulatory ements. This dynamic higher order organization of chromatin is now widely recognized as a mechanism of tissue specific cellular gene regulation. It is our hypothesis that after HIV-1 integration, assembly of proviral DNA into chromatin structures within chromatin domains contribute to cellular regulation of HIV-1 gene expression. To test this hypothesis, we constructed autonomously replicating minichromosomes with matrix attachment regions derived from specific cellular gene clusters flanking the HIV-1 LTR. We show that the 5' and 3' MARs of the serine protease gene cluster CGL-1 (each of which contain a single topoisomerase II cleavage site) downregulate the basal expression from the HIV-1 LTR in a tissue specific manner.
Publication Types:
Keywords:
- Base Sequence
- Chromatin
- DNA
- DNA-Binding Proteins
- HIV Long Terminal Repeat
- HIV-1
- Matrix Attachment Regions
- Multigene Family
- Nuclear Matrix
- genetics
- metabolism
Other ID:
UI: 102216103
From Meeting Abstracts