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EMBO J. least one histone deacetylase. These results suggest that chromatin remodeling, including histone acetylation and chromatin disruption, is usually important for T3 regulation of the HIV-1 LTR in vivo. Human immunodeficiency virus type 1 (HIV-1) is responsible for the development of AIDS and AIDS-related complex (ARC) (56). After acute infection, HIV-1 maintains latency for many years, but the mechanism of its reactivation to cause AIDS and ARC remains largely unclear. It has been suggested that viral reactivation involves complex interactions among chromatin-associated proviral DNA, cellular transcription factors, and viral proteins (11). A critical factor in viral reactivation is the transcription of the viral genome, which is usually directed by the long terminal repeat (LTR). Numerous studies have identified essential DNA elements within the LTR as well as many host and viral proteins for the transcriptional activation of the LTR in vitro and in tissue culture cells (35, 56). The DNA elements important for CXCL5 the LTR activity are located between ?454 and +184, where +1 is the transcription start site. This region contains the TATA box and binding sites for host transcription factors Sp1 and NF-B, etc. (Fig. ?(Fig.11). Open in BRD 7116 a separate window FIG. 1. Schematic representation of the LTR promoter plasmids. pHL10 contained the HIV-1 LTR promoter region from ?107 to +81 in front of a 300-bp CAT reporter fragment in pBluescript KS(?) vector. The promoter fragment included two NF-B sites, three Sp1 sites, and a TATA box followed by a regulatory TAR sequence. Two TREs are located in the regions made up of the NF-B and Sp1 binding sites (NF-B TRE and Sp1 TRE). The Sp1 TRE is usually a stronger TRE than the NF-B TRE (17). The involvement of multiple host factors in HIV-1 transcription suggests that HIV-1 BRD 7116 propagation and pathological progression of AIDS and ARC are likely to be influenced by physiological conditions that affect the availability and function of host factors. Studies on thyroid hormone (T3) levels in AIDS and ARC patients suggest that T3 may affect disease development (27, 51). BRD 7116 The biological effects of T3 are presumed to be mainly mediated by T3 receptors (TRs), which are high-affinity T3-binding nuclear proteins (7, 38, 44, 59). TRs belong to the superfamily of nuclear hormone receptors, with two subfamilies of TRs in vertebrates, TR and TR (12, 28, 52, 70). Transcriptional activation by T3 requires the binding of TRs, most likely as heterodimers with 9-TR function in frog oocytes (62). The role of T3 in LTR regulation is usually supported by several reports demonstrating the binding of TRs to a region of the LTR that contains the binding sites for Sp1 and NF-B in vitro (8, 17, 41, 67). Surprisingly, Rahman et al. (41) reported that TR alone activates the LTR while the addition of T3 reverses this effect, which contrasts findings by us (17) and other groups (8, 67). One possible explanation may be the use of different model systems. In our study, we took advantage of the ability of frog oocytes to replicate and chromatinize exogenous single-stranded DNA (ssDNA) in a process that mimics the process in normal somatic cells (1). We microinjected ssDNA made up of the LTR promoter into oocytes that had or had not been preinjected with the mRNAs encoding a TR and an RXR. Our studies revealed that TR/RXR represses the LTR in a chromatin context in the absence of T3. The addition of T3 reverses this repression and.