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  • 1
    Electronic Resource
    Electronic Resource
    Sp1 Trans-Activation of Cell Cycle Regulated Promoters Is Selectively Repressed by Sp3 (1995)
    s.l. : American Chemical Society
    Biochemistry 34 (1995), S. 16503-16508 
    Details
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/bi00050a034
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  • 2
    Electronic Resource
    Electronic Resource
    Activation of a cell-cycle-regulated histone gene by the oncogenic transcription factor IRF-2 (1995)
    [s.l.] : Nature Publishing Group
    Nature 377 (1995), S. 362-365 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] To confirm the functional role of HiNF-M, we have introduced a series of specific mutations within the H4 promoter site II, a protein-DNA interaction site established by in vivo genomic footprinting7. Several protein factors interact with site II (ref. 3), including HiNF-M, HiNF-P and HiNF-D, a ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/377362a0
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  • 3
    Electronic Resource
    Electronic Resource
    The osteocalcin gene: a model for multiple parameters of skeletal-specific transcriptional control (1997)
    Springer
    Molecular biology reports 24 (1997), S. 185-196 
    Details
    ISSN: 1573-4978
    Keywords: chromatin structure ; differentiation ; nuclear matrix ; osteoblast ; transcription ; vitamin D
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Influences of promoter regulatory elements that are responsive to basal and tissue-restricted transactivation factors, steroid hormones, growth factors and other physiologic mediators has provided the basis for understanding regulatory mechanisms contributing to developmental expression of osteocalcin, tissue specificity and biological activity (reviewed in [1–3]). These regulatory elements and cognate transcription factors support postproliferative transcriptional activation and steroid hormone (e.g. vitamin D) enhancement at the onset of extracellular matrix mineralization during osteoblast differentiation. Three parameters of nuclear structure contribute to osteocalcin gene transcriptional control. The linear representation of promoter elements provides competency for physiological responsiveness within the contexts of developmental as well as phenotype-dependent regulation. Chromatin structure and nucleosome organization reduce distances between independent regulatory elements providing a basis for integrating components of transcriptional control. The nuclear matrix supports gene expression by imposing physical constraints on chromatin related to three dimensional genomic organization. In addition, the nuclear matrix facilitates gene localization as well as the concentration and targeting of transcription factors. Several lines of evidence are presented which are consistent with involvement of multiple levels of nuclear architecture in tissue-specific gene expression during differentiation. Growth factor and steroid hormone responsive modifications in chromatin structure, nucleosome organization and the nuclear matrix are considered which influence transcription of the bone tissue-specific osteocalcin gene during progressive expression of the osteoblast phenotype.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006803615430
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  • 4
    Electronic Resource
    Electronic Resource
    Nuclear matrix associated DNA-binding proteins of ocular lens epithelial cells (1998)
    Springer
    Molecular biology reports 25 (1998), S. 13-19 
    Details
    ISSN: 1573-4978
    Keywords: gene expression ; nuclear matrix proteins ; ocular lens epithelial cells ; transcription factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Association of transcription factors with the nuclear matrix represents a mechanism by which nuclear architecture may influence transcriptional control of gene expression. This investigation examines nuclear matrix associated proteins (NMP's) isolated from ocular lens epithelial cells by monitoring DNA binding activities using consensus oligonucleotides recognized by the transcription factors YY1, AML-1, AP-1, SP-1 and ATF. The nuclear matrix fractions tested included an immortilized human lens epithelial cell line containing the SV40 large T-antigen, and two mouse lens epithelial cell lines derived from either a normal mouse or a cataract mouse. A rabbit epidermal epithelial cell line and HeLa cells were also included in this study for comparison. The data from these experiments reveal that ubiquitously represented and tissue restricted regulatory proteins are associated with nuclear matrix of lens epithelial cells. The functional significance of the nuclear matrix association of these transcription factors remains to be determined. However, our findings raise the possibility that the transcription factors associated with the nuclear matrix could have specific roles in gene regulation and eye tissue development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006886110771
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  • 5
    Electronic Resource
    Electronic Resource
    The integrated activities of IRF-2 (HiNF-M), CDP/cut (HiNF-D) and H4TF-2 (HiNF-P) regulate transcription of a cell cycle controlled human histone H4 gene: mechanistic differences between distinct H4 genes (1998)
    Springer
    Molecular biology reports 25 (1998), S. 1-12 
    Details
    ISSN: 1573-4978
    Keywords: histone H4 ; cell cycle ; interferon regulatory factor ; homeodomain protein ; transcription
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Maximal transcription of a prototypical cell cycle controlled histone H4 gene requires a proliferation-specific in vivo genomic protein/DNA interaction element, Site II. Three sequence-specific transcription factors interact with overlapping recognition motifs within Site II: interferon regulatory factor IRF-2 (HiNF-M), the putative H4 subtype-specific protein H4TF-2 (HiNF-P), and HiNF-D which represents a complex of the homeodomain protein CDP/cut, CDC2, cyclin A and pRB. However, natural sequence variation in the Site II sequences of different human H4 genes abolishes binding of specific trans-acting factors; the functional consequences of these variations have not been investigated. To address the precise contribution of H4 promoter factors to the level of H4 gene transcription, we performed a systematic mutational analysis of Site II transcriptional motifs. These mutants were tested for ability to bind each of the Site II cognate proteins, and subsequently evaluated for ability to confer H4 transcriptional activity using chimeric H4 promoter/CAT fusion constructs in different cell types. We also analyzed the effect of over-expressing IRF-2 on CAT reporter gene expression driven by mutant H4 promoters and assessed H4 transcriptional control in cells nullizygous for IRF-1 and IRF-2. Our results show that the recognition sequence for IRF-2 (HiNF-M) is the dominant component of Site II and modulates H4 gene transcription levels by 3 fold. However, the overlapping recognition sequences for IRF-2 (HiNF-M), H4TF-2 (HiNF-P) and CDP/cut (HiNF-D) together modulate H4 gene transcription levels by at least an order of magnitude. Thus, maximal activation of H4 gene transcription during the cell cycle in vivo requires the integrated activities of multiple transcription factors at Site II. We postulate that the composite organization of Site II supports responsiveness to multiple signalling pathways modulating the activities of H4 gene transcription factors during the cell cycle. Variations in Site II sequences among different H4 genes may accomodate differential regulation of H4 gene expression in cells and tissues with unique phenotypic properties.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006888731301
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  • 6
    Electronic Resource
    Electronic Resource
    The homeodomain transcription factor CDP/cut interacts with the cell cycle regulatory element of histone H4 genes packaged into nucleosomes (1999)
    Springer
    Molecular biology reports 26 (1999), S. 185-194 
    Details
    ISSN: 1573-4978
    Keywords: cell cycle ; chromatin ; histone ; homeodomain ; nucleosome ; tanscription
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The homeodomain transcription factor CDP/cut contains four separate DNA binding domains and interacts with large segments of DNA. Thus, CDP/cut has the potential to function as an architectural protein and perhaps to support modifications in chromatin structure and nucleosomal organization. To begin to examine the ability of CDP/cut to interact with chromatin, we analyzed binding of CDP/cut to the histone H4 gene promoter (−90 to +75) reconstituted into nucleosome cores. The −90 to +75 region encompasses the cell cycle regulatory element (Site II) that controls histone H4 gene transcription, a CDP/cut binding site and a nuclease hypersensitive region. Using electrophoretic mobility shift assays and DNase I footprinting experiments, we show that CDP/cut specifically interacts with its recognition motif in a nucleosomal context without displacing the nucleosome core. The competency of CDP/cut to interact with nucleosomes suggests that this transcription factor may facilitate chromatin remodeling in response to cell cycle regulatory and/or developmental cues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007058123699
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  • 7
    Electronic Resource
    Electronic Resource
    Histone H4 proximal promoter mediates a complex transcriptional response during differentiation of 3T3L1 adipocytes (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 163 (1995), S. 312-320 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We have investigated the promoter element(s) required by the cell cycle regulated FO108 human histone H4 gene for control of gene expression during adipocyte proliferation and differentiation. Stable 3T3L1 cell lines were established that express fusion genes in which the histone H4 promoter is joined to chloramphenicol acetyltransferase (cat) as a reporter gene. Expression of the H4CAT fusion genes was monitored in proliferating and confluent 3T3L1 preadipocytes and in differentiating 3T3L1 adipocytes. The results indicate that the H4 cell cycle element (CCE), which mediates S phase-specific stimulation of H4 gene transcription, is not required for transcriptional regulation during differentiation. Instead, a minimal H4 promoter (nucleotides -46 to -11) is sufficient to mediate the complex transcriptional response of H4 gene expression observed during the process of adipocyte differentiation of 3T3L1 cells. In addition, the data suggest that down-regulation of histone gene expression during cellular differentiation may be mediated by passive inactivation of the promoter due to loss of positive regulatory factor(s). © 1995 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcp.1041630212
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  • 8
    Electronic Resource
    Electronic Resource
    HiNF-D (CDP-cut/CDC2/cyclin A/pRB-complex) influences the timing of IRF-2-dependent cell cycle activation of human histone H4 gene transcription at the G1/S phase transition (1998)
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 177 (1998), S. 453-464 
    Details
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Cell cycle control of histone H4 gene transcription is mediated by the multipartite promoter domain H4-Site II, which supports transcriptional activation at the G1/S phase transition and modulates basal H4 gene transcription. Proliferation-specific transcription is determined by the integrated activities of three distinct promoter factors interacting with H4-Site II: the interferon regulatory factor IRF-2 (synonymous with HiNF-M), HiNF-D (a complex between the homeodomain protein CDP-cut and the cell cycle mediators CDC2, cyclin A and pRB), as well as HiNF-P/H4TF-2. However, the contribution of HiNF-D to the enhancement and/or suppression of H4 gene transcription at specific cell cycle stages remains to be established. We used a panel of synchronized HeLa S3 cell lines containing stably integrated H4 promoter/CAT reporter gene constructs with mutations in H4-Site II. The temporal regulation of CAT mRNA accumulation under the control of the H4 promoter was analyzed by RNase protection analysis. Our main finding is that mutation of the HiNF-D/CDP-cut binding site alters the timing of histone gene activation during the cell cycle. Furthermore, our data indicate that HiNF-P/H4TF-2 may functionally compensate for HiNF-M/IRF-2 at Site II to regulate histone H4 gene transcription in HeLa S3 cervical carcinoma cells during early S phase. We postulate that HiNF-D (CDP-cut/cyclin A/CDC2/pRB containing complex) promotes HiNF-M/IRF-2 (and/or HiNF-P/H4TF-2) dependent histone H4 gene activation at the G1/S phase transition and attenuates H4 gene transcription at later cell cycle stages. The mechanistic division in the gene regulatory functions of the three H4-Site II binding proteins may ensure that histone H4 gene expression is stringently coupled with the onset of S phase in response to growth factor/cytokine-induced cell cycle progression. J. Cell. Physiol. 177:453-464, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Proximal promoter binding protein contributes to developmental, tissue-restricted expression of the rat osteocalcin gene (1995)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 57 (1995), S. 90-100 
    Details
    ISSN: 0730-2312
    Keywords: osteocalcin ; homeodomain protein ; osteoblasts ; transcriptional regulation ; bone specific ; developmental ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Osteocalcin is a 6 kD tissue-specific calcium binding protein associated with the bone extracellular matrix. The osteocalcin gene is developmentally expressed in postproliferative rat osteoblasts with regulation at least in part at the transcriptional level. Multiple, basal promoter and enhancer elements which control transcriptional activity in response to physiological mediators, including steroid hormones, have been identified in the modularly organized osteocalcin gene promoter. The osteocalcin box (OC box) is a highly conserved basal regulatory element residing between nucleotides -99 and -76 of the proximal promoter. We recently established by in vivo competition analysis that protein interactions at the CCAAT motif, which is the central core of the rat OC box, are required for support of basal transcription [Heinrichs et al. J Cell Biochem 53:240-250, 1993]. In this study, by the combined utilization of electrophoretic mobility shift analysis, UV cross linking, and DNA affinity chromatography, we have identified a protein that binds to the rat OC box. Results are presented that support involvement of the OC box-binding protein in regulating selective expression of the osteocalcin gene during differentiation of the rat osteoblast phenotype and suggest that this protein is tissue restricted.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240570110
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  • 10
    Electronic Resource
    Electronic Resource
    In vivo occupancy of histone gene proximal promoter elements reflects gene copy number-dependent titratable transactivation factors and cross-species compatibility of regulatory sequences (1995)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 57 (1995), S. 191-207 
    Details
    ISSN: 0730-2312
    Keywords: histone gene transcription ; chromosome ; H4 gene ; C127 cell ; titratable transcription factors ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: To assess systematically the structural and functional aspects of histone gene transcription within a chromosomal context, we stably integrated an extensive set of human histone H4 gene constructs into mouse C127 cells. Levels of expression were determined by S1 nuclease protection assays for multiple mouse monoclonal cell lines containing these human H4 genes. For each cell line, we quantitated the number of integrated human H4 genes by Southern blot analysis. The results indicate that the expression of the human H4 gene is in part copy number dependent at low gene dosages. However, the level of expression varies among different cell lines containing similar numbers of copies of the same H4 gene construct. This result suggests that position-dependent chromosomal integration effects contribute to H4 gene transcription, consistent with the roles of long-range gene organization and nuclear architecture in gene regulation. At high copy number, the level of human H4 gene expression per copy decreased, and endogenous mouse H4 mRNA levels were also reduced. Furthermore, in vivo occupancy at the human H4 gene immediate 5′ regulatory elements, as defined by genomic fingerprinting, showed copy number-dependent protein/DNA interactions. Hence, human and mouse H4 genes compete for titratable transcription factors in a cellular environment. Taken together, these results indicate cross-species compatibility and suggest limited representation in vivo of the factors involved in regulating histone H4 gene transcription.
    Additional Material: 12 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240570204
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