The nuclear matrix is the site of glucocorticoid receptor complex action in the nucleus

Kirsch, Ted M.; Miller-Diener, A; Litwack, Gerald

doi:10.1016/0006-291x(86)91126-5

Cited by 27 publications

(10 citation statements)

References 18 publications

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“…Several reports demonstrated the GR association with the nuclear matrix (25,26). Tang and DeFranco (49) show a dramatic increase in GR binding to the nuclear matrix in ATPdepleted cells, and they found the DNA binding domain of GR involved in this interaction.…”

Section: Discussionmentioning

confidence: 99%

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The Glucocorticoid Receptor Is Associated with the RNA-binding Nuclear Matrix Protein hnRNP U

Eggert

Michel

Schneider

et al. 1997

Journal of Biological Chemistry

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The glucocorticoid receptor (GR) is a ligand-dependent transcription factor that is able to modulate gene activity by binding to its response element, interacting with other transcription factors, and contacting several accessory proteins such as coactivators. Here we show that GRIP120, one of the factors we have identified to interact with the glucocorticoid receptor, is identical to the heterogeneous nuclear ribonucleoprotein U (hnRNP U), a nuclear matrix protein binding to RNA as well as to scaffold attachment regions. GR⅐hnRNP U complexes were identified by blotting and coimmunoprecipitation. The subnuclear distribution of GR and hnRNP U was characterized by indirect immunofluorescent labeling and confocal laser microscopy demonstrating a colocalization of both proteins. Using a nuclear transport-deficient deletion of hnRNP U, nuclear translocation was seen to be dependent on GR and dexamethasone. Transient transfections were used to identify possible interaction domains. Overexpressed hnRNP U interfered with glucocorticoid induction, and the COOH-terminal domains of both proteins were sufficient in mediating the transcriptional interference. A possible functional role for this GR binding-protein in addition to its binding to the nuclear matrix, to RNA, and to scaffold attachment regions is discussed.The nuclear matrix is involved in the structural organization of the chromatin and the integrity of the nucleus. In addition, DNA replication, RNA processing, and gene transcription are connected to the nuclear matrix, suggesting matrix interactions with chromatin and transcription factors. Chromatin binding to the nuclear matrix during replication has been reported as well as the enrichment of transcribed genes in this nuclear subcompartment (1-3). The DNA-nuclear matrix interaction seems to be mediated by chromatin-associated proteins such as topoisomerase II (4, 5), the lamina-associated attachment region-binding protein (6), and hnRNP U 1 (7,8). These proteins are capable of binding to the A/T-rich scaffold attachment regions (5, 7, 8 -11). HnRNP U belongs to the heterogeneous nuclear ribonucleoproteins that are abundant in the eukaryotic cell nucleus. They are believed to be involved in transcription by participating in pre-mRNA processing (12).The glucocorticoid receptor (GR) belongs to the superfamily of steroid hormone receptors, which are ligand-dependent transcription factors (13). They are known to modulate gene transcription by binding to hormone response elements. In addition, several studies have led to the conclusion that interactions of the receptor molecule with other nuclear proteins are important (14). In general, these proteins could be divided into three classes: (i) components of the basal transcription machinery; (ii) other transcription factors; and (iii) proteins that interact with the nuclear receptors and transmit the gene regulatory signal to other components of the transcriptional machinery (15). Several of these last factors have been described which function as coactivators, e.g. R...

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Section: Discussionmentioning

confidence: 99%

“…Because steroid hormone receptors are found to be localized to the nuclear matrix (22)(23)(24)(25)(26)(27)(28), this gave rise to the idea of a functional interaction between nuclear transcription factors and structural components of the nuclear matrix. In our experiments we identified the nuclear matrix protein hnRNP U to be complexed in vivo with the GR.…”

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confidence: 99%

The Glucocorticoid Receptor Is Associated with the RNA-binding Nuclear Matrix Protein hnRNP U

Eggert

Michel

Schneider

et al. 1997

Journal of Biological Chemistry

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“…This and similar preparations served in much important research and established the matrix as a participant in important nuclear events (16)(17)(18)(19)(20)(21)(22)(23). The preparations were particularly useful for the early specific hormone receptor studies (18,25,26). However, the nuclear matrix remained invisible in the conventional electron micrographs, provoking further skepticism concerning whether the matrix really existed.…”

Section: The Core Filaments Of the Nuclear Matrixmentioning

confidence: 99%

Rethinking cell structure.

Penman

1995

Proc. Natl. Acad. Sci. U.S.A.

151

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Cell structure, emerging from behind the veil of conventional electron microscopy, appears far more complex than formerly realized. The standard plastic-embedded, ultrathin section can image only what is on the section surface and masks the elaborate networks of the cytoplasm and nucleus. Embedment-free electron microscopy gives clear, highcontrast micrographs of cell structure when combined with removal of obscuring material such as soluble proteins. The resinless ultrathin section is the technique of choice; it is simple and inexpensive, and it uses ordinary electron microscopes. The resulting pictures reveal a world of complex cell structure and function. These images necessarily change our conception of the cytoskeleton, nuclear matrix, mitosis, and the relation of membranes to cytostructure.The observational instruments of an experimental science often delineate its most fundamental ideas. In astronomy, every pivotal innovation in teloscopy literally recasts the cosmos: the simple Galilean telescope's discovery of Jupiter's moons was an unparalleled liberation from static, heliocentric heavens of crystalline spheres. Today, radio and y-ray telescopes give us an unsettled universe of neutron stars and black holes. In like manner, biology owes many of its basic concepts to a single class of instruments that reveal the invisible. The microscopes of Leuwenhoeck and Hooke first showed cells, and our notions of cell structure have evolved with improvements in light and electron optical instruments. Given the profound importance of microscopy to cell biology thought, it is quite surprising that the most powerful magnifying instrument of all, the transmission EM, affords a very truncated view of reality.Cell biology has long labored under a serious misperception of cell structure since conventional electron micrographs do not show most of the cell's architectural components. This is not an intrinsic technical weakness of electron imaging, however, and recent, very simple EM techniques give a far more accurate and detailed picture of cell structure. This review briefly explains the problem with conventional EM and how it is solved. Examples of the resulting EM images show that they differ profoundly from the customary picture of internal cell architecture.

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“…A great number of studies (for reviews see Verheijen et al, 1988;Gasser et al, 1989) have led to the conclusion that important nuclear processes like DNA replication (Jackson and Cook, 1986), RNA transcription (Jackson and Cook, 1985 a) and DNA loop attachment (Nelson et al, 1986;Gasser and Laemmli, 1987) are at least transiently associated with the nuclear matrix, although contradictory results have been reported (Roberge et al, 1988). Furthermore, it is likely that several other nuclear entities like ultraviolet-induced DNA repair (McCready and Cook, 1984;Mullenders et al, 1988), poly(ADP4bose) metabolism (Alvarez-Gonzalez and Ringer, 1988;Golderer et al, 1991), steroid receptor complex action (Kirsch et al, 1986) and proto-oncogene proteins (Waitz and Loidl, 1991) are located at the nuclear matrix.…”

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Nuclear matrix of the lower eukaryote Physarum polycephalum and the mammalian epithelial LLC‐PK₁ cell line

Eberharter

Grabher

Gstraunthaler

et al. 1993

European Journal of Biochemistry

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Agarose-encapsulated nuclear matrix preparations of the lower eukaryote Physarum polycephalum and the mammalian renal epithelial LLC-PKJ cell line were analyzed after various experimental protocols with respect to the protein composition. The effect of the mode of deproteinization (2 M NaC1,0.25 M ammonium sulfate or 25 mh4 lithium diiodosalicylate), presence of 2-mercaptoethanol, Ca", Cu2+, chelating agents, the sequence of protein extraction and nuclease digestion, the use of RNase, the temperature at which the experimental manipulations were performed and the use of hypotonic or isotonic conditions was investigated. No significant differences in the final nuclear matrix composition could be observed, regardless of the experimental procedure applied. In Physarum, the major nuclear matrix proteins range over 12-70 kDa with prominent bands at 24, 31, 37 and 45 kDa; the proteins of the matrix in U C -P K J cells extend predominantly over 40-80 kDa.Furthermore, no essential differences in the protein composition could be observed when type I and type I1 nuclear matrices from the highly differentiated LLC-PK, cell line were compared. The same was found for analogous matrix preparations of Physarum. Therefore, in both systems a distinction between type I/II matrix is questionable. Immunoblotting of the matrix preparations with a variety of antibodies against intermediate filament proteins and with antinuclear autoantibodies revealed the presence of intermediate filament proteins as components of the nuclear matrix. We conclude that the nuclear matrix represents a much more stable and reproducible structure than has been proposed so far, largely independent of changes in the preparation protocol.

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The nuclear matrix is the site of glucocorticoid receptor complex action in the nucleus

Cited by 27 publications

References 18 publications

The Glucocorticoid Receptor Is Associated with the RNA-binding Nuclear Matrix Protein hnRNP U

The Glucocorticoid Receptor Is Associated with the RNA-binding Nuclear Matrix Protein hnRNP U

Rethinking cell structure.

Nuclear matrix of the lower eukaryote Physarum polycephalum and the mammalian epithelial LLC‐PK₁ cell line

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The nuclear matrix is the site of glucocorticoid receptor complex action in the nucleus

Cited by 27 publications

References 18 publications

The Glucocorticoid Receptor Is Associated with the RNA-binding Nuclear Matrix Protein hnRNP U

The Glucocorticoid Receptor Is Associated with the RNA-binding Nuclear Matrix Protein hnRNP U

Rethinking cell structure.

Nuclear matrix of the lower eukaryote Physarum polycephalum and the mammalian epithelial LLC‐PK1 cell line

Contact Info

Product

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Nuclear matrix of the lower eukaryote Physarum polycephalum and the mammalian epithelial LLC‐PK₁ cell line