Nuclear matrix and transcriptional activity of the mouse α-globin gene

Kirov, N.; Djondjurov, Lalio; Tsanev, Roumen

doi:10.1016/0022-2836(84)90029-9

Cited by 52 publications

(12 citation statements)

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“…This provides a plausible mechanism by which an enormous length of DNA can be ordered spatially during DNA replication such that the daughter strands remain untangled yet coupled in a precise fashion for separation during mitosis (see Figure 2). In addition, the demonstration that newly synthesized hnRNA and its processing intermediates are associated with the insoluble nuclear matrix (18,43,87,94,95,106,109,112,138,162) and the discovery that certain actively transcribed genes are preferentially associated with the nuclear matrix (44,47,50,97,100,113,117,121,136,137,(146)(147)(148) have done much to further our understanding of the role of structural organization in cellular function. The nuclear matrix appears to be a major site of steroid hormone receptor binding in the nucleus (5, 6, 9-16, 35, 46, 54,63, 79, 130, 13 4, 144, 156, 168, 169); this is consistent with the role of steroid hormones in stimulating hnRNA synthesis, a process that appears to occur in association with the nuclear matrix.…”

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confidence: 99%

The Role of the Nuclear Matrix in the Organization and Function of Dna

Nelson¹,

Pienta²,

Barrack³

et al. 1986

Annu. Rev. Biophys. Biophys. Chem.

331

118

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confidence: 99%

The Role of the Nuclear Matrix in the Organization and Function of Dna

Nelson¹,

Pienta²,

Barrack³

et al. 1986

Annu. Rev. Biophys. Biophys. Chem.

331

118

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“…This question has already been discussed by Kaufmann et al (1981), Kirov et al (1984) and Djondjurov et al (1986). We are convinced, however, that even if we are dealing with secondarily formed structures, they do not arise accidentally.…”

Section: Discussionmentioning

confidence: 71%

Intranuclear compartmentalization of transcribed and nontranscribed c‐myc sequences in Namalva‐S cells

Andreeva

Markova

Loidl

et al. 1992

European Journal of Biochemistry

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This investigation is centered on the intranuclear localization of transcribed and nontranscribed c-myc sequences in human Namalva-S cells bearing t(8 ;14) translocation. Southern hybridization showed that the breakpoint in the truncated allele of c-myc lies outside the characteristic 12.8-kbp EcoRI fragment: as Northern analysis indicated, this reorganization induces a high level of c-myc transcription. Following high-salt treatment, EcoRI digestion and centrifugation, isolated nuclei from the same cells are separated into two residual fractions: a heavier P fraction including nuclear matrix structures and a light S fraction representing dehistonized chromatin fibres. Comparative hybridization experiments revealed that the above procedure separates the c-myc sequences between the two fractions. To locate the site of intranuclear c-myc transcription, we performed run-on experiments with two fractions, topologically analogous to the residual P and S fractions but maintaining the original chromatin organization. These experiments indicated that chromatin P fraction harbours actively transcribed c-myc sequences while chromatin S harbours nontranscribed ones. Further experiments have clarified that the transcribed c-myc sequences are firmly bound to the matrix by multiple attachment sites, arranged throughout the entire gene locus. It was found, moreover, that at the site of attachment the interaction between DNA and the matrix components is realized via proteins. Controls with the P-globin gene, which is constitutively nonexpressed in Namalva-S cells but upon induction is highly expressed in murine erythroleukemia cells, completely confirmed the conclusion we had made for the intranuclear localization of c-myc. Thus the experiments presented here support the more common idea that the transcribed and nontranscribed sequences are precisely compartmentalized.The proto-oncogene c-myc has been extensively studied during the last few years. This gene is believed to be involved in the regulation of the growth and differentiation in normal cells (Rabbits, 1985;Cole, 1986; Kelly and Siebenlist, 1986). On the other hand, a deregulation of c-myc expression by mechanisms such as chromosomal translocation, retroviral insertion, gene amplification and point mutation, contributes to immortalization and transformation of normal cells (Battey et al., 1983;Cole, 1986;Cory, 1986;Cesarman et al., 1987). In human Burkitt's lymphomas, the c-myc gene locus on chromosome 8 is consistently fused to a region of the immunoglobulin heavy-chain locus in t(8;14) translocations, or to the K t(2;8) or A t(8;22) constant light-chain locus in variant translocations (Manolova et al., 1979;Cory, 1986;Bornkamm et al., 1988). A variety of crossover points have been found in these translocations (Boehm and Rabbitts, 1989). Independently of this variety, the truncated alleles usually exhibit a constitutively elevated expression, while the Correspondence to L. Djondjurov, Institute of Molecular Biology, Bulgarian Academy of Sciences, BG-1113 Sofia, Bulga...

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“…As observed here, not only do the conditions used to generate nuclear matrix induce the formation of matrix-like filaments from hnRNP, but they also render 20 -30% of the protein present in concentrated nuclear extracts insoluble in 2 M NaCl. Thus, high-salt insolubility after experimental manipulation may not adequately reflect the solubility properties of proteins in vivo, and, as shown by others (Kirov et al, 1984;Mirkovitch et al, 1984;Small et al, 1985), it is likely that a wide range of enzymatic activities become artifactually associated with the residual material. In the studies of Mirkovitch et al (1984), glutaraldehyde prefixation was used to prevent protein rearrangement, with the result being an inability to isolate matrix complexes.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Matrix-like Filaments and Fibrogranular Complexes Form through the Rearrangement of Specific Nuclear Ribonucleoproteins

Tan

Wooley

LeStourgeon

2000

MBoC

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The behavior of nuclear pre-mRNA-binding proteins after their nuclease and/or salt-induced release from RNA was investigated. After RNase digestion or salt extraction, two proteins that initially exist as tetramers (A2) 3 B1 in isolated heterogeneous nuclear ribonucleoprotein (hnRNP) complexes quantitatively reassociated to form regular helical filaments ranging in length from 100 nm to Ͼ10 m. In highly magnified preparations prepared for scanning transmission electron microscopy, single filaments have diameters near 18 nm. In conventional negatively stained preparations viewed at low magnification, the diameters of the thinnest filaments range from 7 to 10 nm. At protein concentrations of Ͼ0.1 mg/ml, the filaments rapidly aggregated to form thicker filamentous networks that look like the fibrogranular structures termed the "nuclear matrix." Like the residual material seen in nuclear matrix preparations, the hnRNP filaments were insoluble in 2 M NaCl. Filament formation is associated with, and may be dependent on, disulfide bridge formation between the hnRNP proteins. The reducing agent 2-mercaptoethanol significantly attenuates filament assembly, and the residual material that forms is ultrastructurally distinct from the 7-to 10-nm fibers. In addition to the protein rearrangement leading to filament formation, nearly one-third of the protein present in chromatin-clarified nuclear extracts was converted to salt-insoluble material within 1 min of digestion with RNase. These observations are consistent with the possibility that the residual material termed the nuclear matrix may be enriched in, if not formed by, denatured proteins that function in pre-mRNA packaging, processing, and transport. INTRODUCTIONWhen nuclei are extensively digested with DNase and RNase and extracted with high-salt solutions, an insoluble residue remains that retains the gross architecture of the nucleus (reviewed by Pederson, 1998Pederson, , 2000. The residue, termed the "nuclear matrix," represents a small percentage of the total nuclear protein mass, but it is very heterogeneous in protein composition (Hodge et al., 1977;Staufenbiel and Deppert, 1983;Kuzmina et al., 1984). The major proteins present in the residue are the nuclear lamins, proteins that constitute elements of the metaphase chromosome and interphase nuclear scaffold, nuclear envelope and pore complex proteins, and numerous proteins associated with heterogeneous nuclear ribonucleoprotein (hnRNP) complexes (as discussed and referenced by Pederson, 1998).Among the numerous other proteins present in the residual material are those that have been hypothesized to form a fibrous network or fibrogranular complex (Berezney and Coffey, 1977;Kaufmann et al., 1981;Gallinaro et al., 1983). On the basis of various experimental observations it has been suggested that the matrix functions in interphase nuclei to bind DNA and organize chromatin (Basler et al., 1981;Brasch and Peters, 1985;Nickerson et al., 1997), that actively transcribing genes and nascent transcripts are associated with...

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Nuclear matrix and transcriptional activity of the mouse α-globin gene

Cited by 52 publications

References 36 publications

The Role of the Nuclear Matrix in the Organization and Function of Dna

The Role of the Nuclear Matrix in the Organization and Function of Dna

Intranuclear compartmentalization of transcribed and nontranscribed c‐myc sequences in Namalva‐S cells

Nuclear Matrix-like Filaments and Fibrogranular Complexes Form through the Rearrangement of Specific Nuclear Ribonucleoproteins

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