Journal article
Functional analysis of C/EBP transcription factor binding sites in the SIV LTR
Journal of neurovirology, Vol.12, pp.61-61
01 May 2006
Abstract
To examine functional properties of the CCAAT enhancer binding protein (C/EBP) transcription factor family with respect to human immunodeficiency virus type 1 (HIV-1) pathogenesis and neurologic disease, we have proceeded to characterize the simian immunodeficiency virus (SIV) LTR and the corresponding functional elements that interface with this critical family of regulatory factors. In this regard, studies have been initiated to identify and characterize SIV LTR sequences with affinity for members of the C/EBP family. Electrophorectic mobility shift (EMS) and competition analyses using U-937 monocytic nuclear extracts and purified C/EBP were performed, which demonstrated binding of C/EBP to four of the five potential C/EBP sites in the SIV LTR. The binding sites were designated C/EBP upstream site 1 (US1), upstream site 2 (US2), downstream site 1 (DS1), and downstream site 2 (DS2) located at nucleotide positions -102 to -88, -386 to -373, +131 to +144, and +265 to +280, respectively. Results indicated that C/EBP DS1 and DS2 exhibited relatively high affinity for C/EBP alpha and beta. By comparison, both US1 and US2 exhibited lower affinity for C/EBP, and DNase I footprint analyses confirmed these observations. Additional studies also indicate that US1 and US2 may interact with other transcription factors. Functional analysis of these sites utilizing transient transfection has demonstrated US2, DS1, and DS2 to be repressive in nature while US1 was shown to function as an activating element in cells on the monocytic lineage. Studies will continue to examine the functional impact of the SIV C/EBP sites and their variants on viral gene expression and replication in the SIV/macaque system.
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Details
- Title
- Functional analysis of C/EBP transcription factor binding sites in the SIV LTR
- Creators
- M NonnemacherF KrebsB Wigdahl
- Publication Details
- Journal of neurovirology, Vol.12, pp.61-61
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170488704721