Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
A biochemical and functional analysis of the human T-cell lymphotropic virus type I long terminal repeat region.
Diss Abstr Int [B]; 55(6):2099 1994. Unique Identifier : AIDSLINE ICDB/95615370 Tillmann ME; Pennsylvania State Univ.
Abstract:
Although HTLV-I is a documented etiologic agent of ATL and TSP, the host and viral factors operative during these oncogenic and neuropathogenic processes remain undefined. The HTLV-I-encoded transcriptional trans-activator of the HTLV-I LTR region, Tax, cannot bind directly to DNA suggesting that Tax mediates enhancement utilizing cellular intermediaries, factors which are also critical for basal transcription. The cis-acting Tax-responsive sequences are comprised of three imperfectly repeated 21 bp elements. Non-conservation among the enhancer elements led us to hypothesize that 21 bp repeat-specific DNA-protein interactions may occur between cellular factors and each of the enhancer elements. Furthermore, these interactions may be cell type-dependent. Through electrophoretic mobility shift analyses, we detected both common and enhancer-specific as well as glial cell-specific DNA-protein complexes when cellular factors of immune and nervous system origin were reacted with each 21 bp repeat element. Partial characterization of these complexes indicated that CREB/ATF family members were constituents of the common and glial cell-specific complexes while Sp1 and AP2 were involved in complex formation exclusively with the promoter proximal element. Functional studies examining the role of the promoter proximal element in HTLV-I LTR-directed transcription indicated that this element is functionally unique when compared to the remaining 21 bp repeat elements. In addition to the impact of cellular factors on LTR-directed transcription, viral factors may contribute to the ability of particular LTR isolates to mediate transcription in certain cell types. Nucleotide sequence variations have been noted within both the enhancer region (U3) and the U5 region of the HTLV-I LTR, a region which contains transcriptional repressor sequences. Functional studies examining the role of sequence differences between ATL- and TSP-derived HTLV-I LTR isolates in LTR-directed transcription indicated that sequence variations between isolates impact on the ability of a particular HTLV-I LTR to mediate both basal and Tax-mediated transcription. Collectively, we have demonstrated that regulation of HTLV-I LTR-directed transcription is a complex process which is affected by both variations in cellular and viral factors thus providing new insight into the transcriptional regulation of HTLV-I in cells of immune and nervous system origin. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD94-28219)
Keywords: DNA-Binding Proteins/GENETICS Gene Products, tax/*METABOLISM Human HIV Long Terminal Repeat Nuclear Proteins/METABOLISM Paraparesis, Tropical Spastic/*GENETICS/METABOLISM Transcription Factor, Sp1/GENETICS Transcription Factors/GENETICS/METABOLISM Transcription, Genetic THESIS 951230
M95C3240
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Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
