Transcription Regulatory Complexes Bind the Human T-Cell Leukemia Virus 5′ and 3′ Long Terminal Repeats To Control Gene Expression

Lemasson, Isabelle; Polakowski, Nicholas; Laybourn, Paul J.; Nyborg, Jennifer K.

doi:10.1128/mcb.24.14.6117-6126.2004

Cited by 58 publications

(70 citation statements)

References 52 publications

(47 reference statements)

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“…ChIP Assays, Real-time PCR, and Primers-ChIP assays, real-time PCR, and data analysis were performed as previously described (23,29). PCR primers were as follows: HTLV-1 promoter (Ϫ349/Ϫ81), 5Ј-AA-TGACCATGAGCCCCA/GTGAGGGGTTGTCGTCA-3Ј; luciferase proximal (ϩ708/ϩ804), 5Ј-ATTTATCGGAGTTGCAGTTGCGCC/ AACAAACACTACGGTAGGCTGCGA-3Ј; luciferase distal (ϩ1527/ ϩ1717), 5Ј-TGAAGCGAAGGTTGTGGATCTGGA/AGAAGTGTT-CGTCTTCGTCCCAGT-3Ј; luciferase Region 2 (ϩ799/ϩ1041), 5Ј-C-GCAGTATCCGGAATGATTTGATTGCCA/ACGGATTACCAGG-GATTTCAGTCG-3Ј; pGL3 vector 5Ј (Region 1), 5Ј-GATCGGTGCG-GGCCTCTTCGCTATTA/TCGATAGAGAAATGTTCTGGCACC-TGCACT-3Ј; pGL3 vector 3Ј (Region 3), 5Ј-GGG AGGTGTGGGAG-GTTT/ACCGTATTACCGCCTTTGAGTGAG-3Ј; ␤-globin promoter, 5Ј-TCACACACTTGACCCTGTGCCATA/TTATATGCCCTGT-CCTGGCTCCTT-3Ј.…”

Section: Methodsmentioning

confidence: 99%

“…In previous studies we have examined transcription factor binding and histone modifications at the viral promoter in Tax-expressing, HTLV-1-infected cells (23,29). In this study, we sought to better define the epigenetic changes that occur during Tax-dependent activation of HTLV-1 LTR-directed transcription in vivo.…”

Section: Human T-cell Leukemia Virus Type 1 (Htlv-1)mentioning

confidence: 99%

“…The integrated HTLV-1 promoter is the true physiological substrate for transcription factor binding and Tax transactivation, as the provirus is packaged into nucleosomes following integration into the host cell chromosome. We have used these cells in a previous study to demonstrate mutually exclusive binding of Tax and histone deacetylase complexes at the HTLV-1 promoter (29).…”

Section: Tax Expression Reduces Histone Tail Acetylation Associated Wmentioning

confidence: 99%

“…Using chromatin assembled with core histones lacking their amino-terminal tails and using specific inhibitors of CBP/p300, we have found that CBP/p300 participate in critical chromatin-specific, histone tail-independent acetylation events during transcriptional activation by Tax (28). These data suggest that, in addition to the core histone tails, another target of acetylation by p300 functions in mediating strong Tax transactivation in a chromatin environment.In previous studies we have examined transcription factor binding and histone modifications at the viral promoter in Tax-expressing, HTLV-1-infected cells (23,29). In this study, we sought to better define the epigenetic changes that occur during Tax-dependent activation of HTLV-1 LTR-directed transcription in vivo.…”

mentioning

confidence: 99%

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Tax-dependent Displacement of Nucleosomes during Transcriptional Activation of Human T-Cell Leukemia Virus Type 1

Lemasson

Polakowski

Laybourn

et al. 2006

Journal of Biological Chemistry

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The human T-cell leukemia virus type 1 (HTLV-1) is integrated into the host cell DNA and assembled into nucleosomes. Within the repressive chromatin environment, the virally encoded Tax protein mediates the recruitment of the coactivators CREB-binding protein/p300 to the HTLV-1 promoter, located within the long terminal repeats (LTRs) of the provirus. These proteins carry acetyltransferase activity that is essential for strong transcriptional activation of the virus in the context of chromatin. Consistent with this, the amino-terminal tails of nucleosomal histones at the viral promoter are acetylated in Tax-expressing cells. We have developed a system in which we transfect Tax into cells carrying integrated copies of the HTLV-1 LTR driving the luciferase gene to analyze changes in "activating" histone modifications at the LTR. Unexpectedly, Tax transactivation led to an apparent reduction of these modifications at the HTLV-1 promoter and downstream region that correlates with a similar reduction in histone H3 and linker histone H1. Micrococcal nuclease protection analysis showed that less LTR-luciferase DNA is nucleosomal in Tax-expressing cells. Furthermore, nucleosome depletion correlated with RNA polymerase II recruitment and loss of SWI/SNF. The M47 Tax mutant, deficient in HTLV-1 transcriptional activation, was also defective for nucleosome depletion. Although this mutant formed complexes with CREB and p300 at the HTLV-1 promoter in vivo, it was unable to mediate RNA polymerase II recruitment or SWI/SNF displacement. These results support a model in which nucleosomes are depleted from the LTR and transcribed region during Tax-mediated transcriptional activation and correlate RNA polymerase II recruitment with nucleosome depletion. Human T-cell leukemia virus type 1 (HTLV-1)4 is the etiological agent of adult T-cell leukemia and HTLV-1-associated myelopathy/ tropical spastic paraparesis (1-4). Although not fully understood, the cellular events leading to the onset of both diseases appear to be initiated by the HTLV-1-encoded Tax protein (5). Tax functions as a potent activator of HTLV-1 transcription in part via the formation of a complex with CREB (or other activiting transcription factor/CREB members) and the three CRE enhancer sequences located within the HTLV-1 promoter (6 -8). Tax contributes to the stability of the ternary complex by binding directly to the GC-rich sequences flanking the octanucleotide CREs (9 -12). These sequences, called viral CREs, are absolutely required for strong Tax transcriptional activation of HTLV-1 (13-15). Once associated with the promoter, Tax and CREB form a complex with the cellular coactivators CBP/p300 (16, 17). These coactivators are believed to participate in pre-initiation complex formation, culminating in strong HTLV-1 transcriptional activation (18).The HTLV-1 provirus is integrated into the genome of the infected host cell and assembled into nucleosomes. This chromatin packaging renders promoter DNA less accessible to the binding of transcription factors and ther...

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Section: Methodsmentioning

confidence: 99%

Section: Human T-cell Leukemia Virus Type 1 (Htlv-1)mentioning

confidence: 99%

Section: Tax Expression Reduces Histone Tail Acetylation Associated Wmentioning

confidence: 99%

mentioning

confidence: 99%

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Tax-dependent Displacement of Nucleosomes during Transcriptional Activation of Human T-Cell Leukemia Virus Type 1

Lemasson

Polakowski

Laybourn

et al. 2006

Journal of Biological Chemistry

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“…Indeed, HDAC complexes differ between the 5Ј-and 3Ј-HTLV-1 promoters, with HDAC1 and HDAC2 binding preferentially at the 5Ј-LTR and HDAC3 binding at the 3Ј-LTR. 38 VPA, in addition to the weakly inhibiting catalytic activity of class I HDAC 39 induces proteasomal degradation of HDAC2, unlike other inhibitors, eg, trichostatin A. 40 VPA preferentially releases HDAC2-dependent transcriptional repression and therefore might favor Tax binding at the 5Ј-LTR and sense-strand transcription.…”

mentioning

confidence: 99%

Effects of valproate on Tax and HBZ expression in HTLV-1 and HAM/TSP T lymphocytes

Belrose

Gross

Olindo

et al. 2011

Blood

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IntroductionHuman T-lymphotropic virus-1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/ tropical spastic paraparesis (HAM/TSP). 1,2 Although the majority of HTLV-1-infected individuals remain asymptomatic carriers (ACs), the lifetime cumulative risk of developing ATL or HAM/ TSP is Ͻ 5%. HTLV-1-provirus integrates into the genome of infected cells, predominantly CD4 ϩ CD25 ϩ T lymphocytes, which represent the main reservoir in peripheral blood. 3 HAM/TSP, a central nervous system neuroinflammatory disease, is associated with perivascular and parenchymal infiltration of HTLV-1-infected T cells and activated cytotoxic T lymphocytes (CTLs). 4 A major determinant of HAM/TSP development is the HTLV-1-infected cell burden. The peripheral blood HTLV-1-proviral load is higher in HAM/TSP patients than AC. 5,6 Follow-up studies of HAM/TSP cohorts showed that high provirus loads were associated with rapid disease progression. [7][8][9] Those studies also demonstrated a relative stability of the HTLV-1-proviral load throughout the disease. Set-point provirus load and subsequent HAM/TSP risk are influenced by the cellular immune-response efficiency, 10 although excessive activation of HTLV-1-specific CTLs might become deleterious and contribute to central nervous system tissue damage. 4 Host-pathogen interplay is characterized by very dynamic kinetics, resulting in an equilibrium between the virus-driven clonal expansion of infected T cells 11 and tight control exerted by the immune response. 10 Tax, a transactivator protein encoded by the pX region of the HTLV-1 genome, plays a central role in disease pathogenesis. Tax activates viral transcription and also modulates many cellular signaling pathways involved in T cell activation, cycling, apoptosis or a combination. 12 Tax expression is promitotic and drives CD4 ϩ T-cell proliferation. 13 At the same time, Tax is the immunodominant target recognized by the CTL response. 14 Rapid immune elimination of Tax-expressing cells may explain the poor detection of Tax-gene products (ie, mRNA or protein) in freshly isolated peripheral blood mononuclear cells (PBMCs) from infected patients. 15-18 Short-term culture enables Tax detection and ex vivo conditions might allow Tax-expressing cells to escape immune selective pressure. 19 The current model of HTLV-1 accumulation and persistence supposes 2 steps: first, Tax expression propels CD4 ϩ T cells into cell cycling, which is well documented; and second, silencing of virus expression allows escape from immune surveillance, which remains to be elucidated. Epigenetic mechanisms might participate in silencing of HTLV-1 gene transcription. 20 Use of histone deacetylase (HDAC) inhibitors, such as valproate (2-npropylpentanoic acid, VPA), was postulated to transiently activate virus expression and thereby expose the latent virus reservoir to immune destruction. 21,22 Another avenue of research focuses on negative posttranscriptional regulators of virus expression, eg, pX-encoded Rex and p30 II...

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The human T‐cell leukemia virus type 1 (HTLV‐1): New insights into the clinical aspects and molecular pathogenesis of adult t‐cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV‐associated myelopathy (TSP/HAM)

Shuh

Beilke

2005

Microscopy Res & Technique

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Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus to be identified in the early 1980s. The isolation and identification of a related virus, HTLV-2, and the distantly related human immunodeficiency virus (HIV) immediately followed. Of the three retroviruses, two are associated definitively with specific diseases, HIV, with acquired immune deficiency syndrome (AIDS) and HTLV-1, with adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). While an estimated 10-20 million people worldwide are infected with HTLV-I, infection is endemic in the Caribbean, parts of Africa, southwestern Japan, and Italy. Approximately 4% of HTLV-I infected individuals develop ATLL, a disease with a poor prognosis. The clinical manifestations of infection and the current biology of HTLV viruses with emphasis on HTLV-1 are discussed in detail. The implications for improvements in diagnosis, treatment, intervention, and vaccination are included, as well as a discussion of the emergence of HTLV-1 and -2 as copathogens among HIV-1-infected individuals.

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Transcription Regulatory Complexes Bind the Human T-Cell Leukemia Virus 5′ and 3′ Long Terminal Repeats To Control Gene Expression

Cited by 58 publications

References 52 publications

Tax-dependent Displacement of Nucleosomes during Transcriptional Activation of Human T-Cell Leukemia Virus Type 1

Tax-dependent Displacement of Nucleosomes during Transcriptional Activation of Human T-Cell Leukemia Virus Type 1

Effects of valproate on Tax and HBZ expression in HTLV-1 and HAM/TSP T lymphocytes

The human T‐cell leukemia virus type 1 (HTLV‐1): New insights into the clinical aspects and molecular pathogenesis of adult t‐cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV‐associated myelopathy (TSP/HAM)

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