Cell-cycle-specific interaction of nuclear DNA-binding proteins with a CCAAT sequence from the human thymidine kinase gene.

Knight, Glenn B.; Gudas, Jean M.; Pardee, Arthur B.

doi:10.1073/pnas.84.23.8350

Cited by 72 publications

(36 citation statements)

References 59 publications

(48 reference statements)

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“…Evidence for the existence of multiple forms of CCAATbox-binding proteins has been well documented (8,15,29,40). The heat lability of yCAAT and its lack of dependence on Mg2" for binding suggest that it is distinct from the heat-stable CAT-binding protein described by Graves et al (24) and from CCAAT-binding transcription factor/nuclear factor I (26,49).…”

Section: Discussionmentioning

confidence: 99%

Nuclear proteins that bind the human gamma-globin gene promoter: alterations in binding produced by point mutations associated with hereditary persistence of fetal hemoglobin.

Gumucio¹,

Rood²,

Gray³

et al. 1988

Mol. Cell. Biol.

103

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The molecular mechanisms responsible for the human fetal-to-adult hemoglobin switch have not yet been elucidated. Point mutations identified in the promoter regions of y-globin genes from individuals with nondeletion hereditary persistence of fetal hemoglobin (HPFH) may mark cis-acting sequences important for this switch, and the trans-acting factors which interact with these sequences may be integral parts in the puzzle of y-globin gene regulation. We have used gel retardation and footprinting strategies to define nuclear proteins which bind to the normal -y-globin promoter and to determine the effect of HPFH mutations on the binding of a subset of these proteins. We have identified five proteins in human erythroleukemia cells (K562 and HEL) which bind to the proximal promoter region of the normal -y-globin gene. One factor, yCAAT, binds the duplicated CCAAT box sequences; the -117 HPFH mutation increases the affinity of interaction between yCAAT and its cognate site. Two proteins, -yCAC1 and -yCAC2, bind the CACCC sequence. These proteins require divalent cations for binding. The -175 HPFH mutation interferes with the binding of a fourth protein, yOBP, which binds an octamer sequence (ATGCAAAT) in the normal 'y-globin promoter. The HPFH phenotype of the -175 mutation indicates that the octamer-binding protein may play a negative regulatory role in this setting. A fifth protein, EF'ya, binds to sequences which overlap the octamer-binding site. The erythroid-specific distribution of EFya and its close approximation to an apparent repressor-binding site suggest that it may be important in y-globin regulation.The human fetal-to-adult hemoglobin switch, which normally occurs at birth, is characterized by reduced -y-globin gene expression and increased activity of the adult ,B-and 8-globin genes. Despite major advances in the understanding of the structure of the human hemoglobin genes, the mechanism controlling this developmental switch has remained elusive (28).Clues to the location of important regulatory sequences in the globin genes might be gleaned from the study of naturally occurring mutations associated with abnormal expression of these genes. Such a model is provided by nondeletion hereditary persistence of fetal hemoglobin (HPFH). This syndrome is characterized by elevated expression (5-to 80-fold) of the -y-globin gene in adult life. By sequencing of DNA from affected individuals, several point mutations have been identified in the promoter regions of the overexpressed y-globin genes ( Table 1). The concordance of these point mutations with the HPFH phenotype (9, 61) suggests that they mark important regulatory sequences in the -y-globin genes. In fact, when cloned into expression vectors containing the chloramphenicol acetyltransferase (cat) gene and tested in K562 cells, the mutant promoters direct three-to eightfold overexpression of chloramphenicol acetyltransferase relative to a normal promoter (F. S. Collins, D. M. Bodine, W. K. Lockwood, J. L. Cole, L. Mickley, and T. Ley, Clin. Res. 34:454a, 198...

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Section: Discussionmentioning

confidence: 99%

Nuclear proteins that bind the human gamma-globin gene promoter: alterations in binding produced by point mutations associated with hereditary persistence of fetal hemoglobin.

Gumucio¹,

Rood²,

Gray³

et al. 1988

Mol. Cell. Biol.

103

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“…Harvey et al, 1982;Pelham, 1982;Treisman, 1985;Karin et al, 1984;La Bella et al, 1988) has been augmented in many recent reports by the identification and characterization of the corresponding sequence specific DNA-binding transcription factors (e.g. Knight et al, 1987;Angel et al, 1987;Wu, 1984;Parker and Topol, 1984;Sive and Roeder, 1986;Treisman, 1986). The identification of such cis-and trans-acting components is clearly a prerequisite to the understanding of the basic mechanisms which mediate differential gene expression.…”

Section: Introductionmentioning

confidence: 99%

Direct combinatorial interaction between a herpes simplex virus regulatory protein and a cellular octamer-binding factor mediates specific induction of virus immediate-early gene expression.

1988

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We provide evidence for a novel mechanism of transcriptional regulation in which the immediate-early (IE) transactivating protein of herpes simplex virus, Vmw65, is assembled into a specific DNA-binding complex together with a cellular octamer-binding factor (TRF). The assembly of Vmw65/TRF complex requires not only the core TRF recognition site, but also flanking sequences which are dispensable for TRF binding alone. We show from functional analyses that TRF binding by a motif is required but not sufficient to confer induction on a heterologous promoter, and it is the ability of the motif to allow TRF/Vmw65 complex assembly which correlates with functional activity. Thus, for the induction of HSV IE expression, Vmw65 forms a complex with TRF by recognition of the specific subset of appropriately flanked TRF binding sites present in each of the IE genes. This mechanism may provide a paradigm for the selective utilization of the same transcription factor in differential gene expression.

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“…The NF-1 sites from both adenovirus and BKV compete equally with these protecting proteins, indicating that all three domains are protected by the same or a similar protein that binds to the origin of replication of human adenovirus (32). The prevalence of the NF-1 family of proteins is now well recognized (20,(23)(24)(25)(26)(27)50), and the diversity among the members of this family with respect to molecular weight and biochemical and DNA-binding properties has been suggested (7,14,22). Multiple complexes formed by nuclear factors with a 68-bp repeat were inhibited by the NF-1 binding site from adenovirus and vice versa.…”

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confidence: 99%

Identification of HeLa cell nuclear factors that bind to and activate the early promoter of human polyomavirus BK in vitro.

Chakraborty¹,

Das²

1989

Mol. Cell. Biol.

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Human polyomavirus BK (BKV), an oncogenic DNA virus, differs from other papovaviruses in the organization of the regulatory region and in tissue tropism for kidney cells. The noncoding regulatory region of the viral genome in prototype strains includes three 68-base-pair (bp) repeats, each containing a number of potential regulatory elements. Some of these signals are unique to human papovaviruses, and others are homologous to those identified in many viral and cellular genes. We evaluated the contribution of individual 68-bp repeats to the initiation of transcription from the early promoter in a HeLa cell extract and identified cis-acting elements to which human cellular factors bind to activate transcription. The early promoter with only one copy of the 68-bp repeat could accurately initiate transcription in vitro, but additional copies were required for its stimulation. DNA-binding assays and DNase I protection experiments identified six domains in the regulatory region protected by human cellular factors. Two of these footprints were located within the proximal and distal 68-bp repeats, and one was located at the late side of the repeats. These footprints were centered over a TGGA(N)s_6GCCA core and were produced by a protein of the nuclear factor 1 (NF-1) family. This protein is either identical or similar to that which binds to the high-affinity site at the origin of adenovirus DNA replication. Three other domains, two at the junctions of the 68-bp repeats and one in the late side of the repeats, were partially protected by proteins with AP-1-and Sp-1-like activities. Transcription initiation from the early promoter was drastically reduced when a complete 68-bp repeat or the NF-1 binding site was used as a competitor in the in vitro assay. However, a point mutation within the NF-1 binding site, which reduced NF-1 binding in vitro to a level comparable to that of nonspecific DNA, also eliminated its ability to compete with early transcription. The murine homolog of the AP-1 binding site had a modest effect on in vitro transcription. Our results suggest that, among the multiple HeLa cell nuclear factors, NF-1 acts as a major activator of the early promoter in vitro.BK virus (BKV) is a human polyomavirus that infects most of the world's population by the time of adolescence and is thought to be a causative agent for human cancer (34,36,37,46). It can transform rodent cells, either in living animals or in culture (52-54). Transgenic mice containing the early region of the viral genome develop tumors in tissues commonly affected by this virus (49). In infected individuals, the virus persists in a latent form throughout life and is reactivated by unknown mechanisms when immunity is suppressed naturally or therapeutically (5, 6, 16). Reactivation of this virus has been shown recently to be associated with acute hemorrhagic cystitis (1, 2).Several strains of BKV have been isolated, cloned, and sequenced (3,16,35,41,47,51,55). All of them show extensive homology in protein-coding sequences both with each other and ...

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Cell-cycle-specific interaction of nuclear DNA-binding proteins with a CCAAT sequence from the human thymidine kinase gene.

Cited by 72 publications

References 59 publications

Nuclear proteins that bind the human gamma-globin gene promoter: alterations in binding produced by point mutations associated with hereditary persistence of fetal hemoglobin.

Nuclear proteins that bind the human gamma-globin gene promoter: alterations in binding produced by point mutations associated with hereditary persistence of fetal hemoglobin.

Direct combinatorial interaction between a herpes simplex virus regulatory protein and a cellular octamer-binding factor mediates specific induction of virus immediate-early gene expression.

Identification of HeLa cell nuclear factors that bind to and activate the early promoter of human polyomavirus BK in vitro.

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