Nuclear architecture supports integration of physiological regulatory signals for transcription of cell growth and tissue‐specific genes during osteoblast differentiation

Stein, Gary S.; Wijnen, André J. van; Lian, Jane B.; Bidwell, Joseph P.; Montecino, Martín

doi:10.1002/jcb.240550103

Cited by 43 publications

(28 citation statements)

References 74 publications

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“…In one possible model for MMTV transcription, MARs in both LTRs bind to the nuclear matrix and, as in models proposed for other transcriptional units (39,82), loop out the intervening transcribed region. Cux/CDP and SATB1 bind to the MAR-associated NREs in the MMTV LTR.…”

Section: Discussionmentioning

confidence: 98%

“…It has been suggested that binding to the nuclear matrix is a prerequisite for gene transcription and that MARs function to anchor genes to the nuclear matrix, a structure rich in transcription factors (39,82). In one possible model for MMTV transcription, MARs in both LTRs bind to the nuclear matrix and, as in models proposed for other transcriptional units (39,82), loop out the intervening transcribed region.…”

Section: Discussionmentioning

confidence: 99%

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The Matrix Attachment Region-Binding Protein SATB1 Participates in Negative Regulation of Tissue-Specific Gene Expression

Liu

Bramblett

Zhu

et al. 1997

Molecular and Cellular Biology

113

150

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The nuclear matrix has been implicated in several cellular processes, including DNA replication, transcription, and RNA processing. In particular, transcriptional regulation is believed to be accomplished by binding of chromatin loops to the nuclear matrix and by the concentration of specific transcription factors near these matrix attachment regions (MARs). A number of MAR-binding proteins have been identified, but few have been directly linked to tissue-specific transcription. Recently, we have identified two cellular protein complexes (NBP and UBP) that bind to a region of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) previously shown to contain at least two negative regulatory elements (NREs) termed the promoter-proximal and promoter-distal NREs. These NREs are absent from MMTV strains that cause T-cell lymphomas instead of mammary carcinomas. We show here that NBP binds to a 22-bp sequence containing an imperfect inverted repeat in the promoter-proximal NRE. Previous data showed that a mutation (p924) within the inverted repeat elevated basal transcription from the MMTV promoter and destabilized the binding of NBP, but not UBP, to the proximal NRE. By using conventional and affinity methods to purify NBP from rat thymic nuclear extracts, we obtained a single major protein of 115 kDa that was identified by protease digestion and partial sequencing analysis as the nuclear matrix-binding protein special AT-rich sequence-binding protein 1 (SATB1). Antibody ablation, distamycin inhibition of binding, renaturation and competition experiments, and tissue distribution data all confirmed that the NBP complex contained SATB1. Similar types of experiments were used to show that the UBP complex contained the homeodomain protein Cux/CDP that binds the MAR of the intronic heavy-chain immunoglobulin enhancer. By using the p924 mutation within the MMTV LTR upstream of the chloramphenicol acetyltransferase gene, we generated two strains of transgenic mice that had a dramatic elevation of reporter gene expression in lymphoid tissues compared with reporter gene expression in mice expressing wild-type LTR constructs. Thus, the 924 mutation in the SATB1-binding site dramatically elevated MMTV transcription in lymphoid tissues. These results and the ability of the proximal NRE in the MMTV LTR to bind to the nuclear matrix clearly demonstrate the role of MAR-binding proteins in tissue-specific gene regulation and in MMTV-induced oncogenesis.The nuclear matrix is a network of RNA and nonhistone proteins that serves as a scaffold for loops of chromatin (10,11,64). This matrix has been associated with the regulation of DNA replication, transcription, and RNA processing (for a review, see reference 64). The DNA regions anchoring chromatin to the matrix (called matrix-associated regions [MARs] or scaffold-associated regions) (18) are composed of AT-rich sequences that have a unique structure characterized by high unwinding potential and the formation of a narrow minor groove (1, 52). MARs have been shown to colocal...

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

The Matrix Attachment Region-Binding Protein SATB1 Participates in Negative Regulation of Tissue-Specific Gene Expression

Liu

Bramblett

Zhu

et al. 1997

Molecular and Cellular Biology

113

150

View full text Add to dashboard Cite

show abstract

“…The nuclear matrix has been linked to multiple functions that mediate the control of gene expression within the nucleus (1)(2)(3)(4)(5)(6)(7)(8). This component of the nuclear architecture provides the internal scaffold of the nucleus; it consists of a peripheral lamina-pore complex, an internal filamentous ribonucleoprotein network, and residual nucleoli (2,8).…”

mentioning

confidence: 99%

The nuclear matrix protein NMP-1 is the transcription factor YY1.

Guo

Odgren

Wijnen

et al. 1995

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

160

126

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NMP-1 was initially identified as a nuclear matrix-associated DNA-binding factor that exhibits sequencespecific recognition for the site IV regulatory element of a histone H4 gene. This distal promoter domain is a nuclear matrix interaction site. In the present study, we show that NMP-1 is the multifunctional transcription factor YY1. Gelshift and Western blot analyses demonstrate that NMP-1 is immunoreactive with YY1 antibody. Furthermore, purified YY1 protein specifically recognizes site IV and reconstitutes the NMP-1 complex. Western blot and gel-shift analyses indicate that YY1 is present within the nuclear matrix. In situ immunofluorescence studies show that a significant fraction of YY1 is localized in the nuclear matrix, principally but not exclusively associated with residual nucleoli. Our results confirm that NMP-1/YY1 is a ubiquitous protein that is present in both human cells and in rat osteosarcoma ROS 17/2.8 cells. The finding that NMP-1 is identical to YY1 suggests that this transcriptional regulator may mediate gene-matrix interactions. Our results are consistent with the concept that the nuclear matrix may functionally compartmentalize the eukaryotic nucleus to support regulation ofgene expression.The nuclear matrix has been linked to multiple functions that mediate the control of gene expression within the nucleus (1-8). This component of the nuclear architecture provides the internal scaffold of the nucleus; it consists of a peripheral lamina-pore complex, an internal filamentous ribonucleoprotein network, and residual nucleoli (2, 8). The nuclear matrix plays an important role in higher-order organization of chromatin and the tethering of actively transcribed genes via matrix-associated regions (MARs) or scaffold-attached regions (SARs) (9-18). Involvement of the nuclear matrix in RNA processing has been demonstrated; heterogeneous nuclear RNAs, small nuclear RNAs, and RNA processing intermediates are enriched in the nuclear matrix; ribonucleoprotein particles are components of nuclear matrix structure (19)(20)(21)(22) (35) have shown that c-myc inhibits both the repressor and activator functions of YY1. In the c-fos promoter YY1 appears to act by bending DNA to regulate contact between other factors (37). Thus, YY1 has been implicated in several possible functional roles related to transcription.In this study, we unequivocally establish that the nuclear matrix protein NMP-1 is the transcriptional regulator YY1 and demonstrate that NMP-1/YY1 is localized to the nuclear matrix in situ as well as by biochemical analyses. MATERIALS AND METHODSNuclear Protein Preparations. Nuclear extracts were prepared as described (38) The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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“…Although specific MAR-binding proteins have been identified (18,77), their role in mediating the tissue-and cell-type-specific binding of active genes to the nuclear matrix is not understood. A number of transcription factors have been found to be associated with the nuclear matrix (6,73,76) and appear to differentially partition between the matrix and an extractable compartment of the nucleus, depending on such variables as tissue type and growth conditions (70). Therefore, it seems likely that specific mechanisms exist to regulate the exchange of transcription factors between the nuclear matrix and soluble compartments of the nucleus.…”

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confidence: 99%

ATP-Dependent Release of Glucocorticoid Receptors from the Nuclear Matrix

Tang

DeFranco

1996

Molecular and Cellular Biology

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Glucocorticoid receptors (GRs) have the capacity to shuttle between the nuclear and cytoplasmic compartments, sharing that trait with other steroid receptors and unrelated nuclear proteins of diverse function. Although nuclear import of steroid receptors, like that of nearly all other karyophilic proteins examined to date, requires ATP, there appear to be different energetic requirements for export of proteins, including steroid receptors, from nuclei. In an attempt to reveal which steps, if any, in the nuclear export pathway utilized by steroid receptors require ATP, we have used indirect immunofluorescence to visualize GRs within cells subjected to a reversible ATP depletion. Under conditions which lead to >95% depletion of cellular ATP levels within 90 min, GRs remain localized within nuclei and do not efflux into the cytoplasm. Under analogous conditions of ATP depletion, transfected progesterone receptors are also retained within nuclei. Importantly, GRs which accumulate within nuclei of ATP-depleted cells are distinguished from nuclear receptors in metabolically active cells by their resistance to in situ extraction with a hypotonic, detergent-containing buffer. GRs in ATP-depleted cells are not permanently trapped in this nuclear compartment, as nuclear receptors rapidly regain their capacity to be extracted upon restoration of cellular ATP, even in the absence of de novo protein synthesis. More extensive extraction of cells with high salt and detergent, coupled with DNase I digestion, established that a significant fraction of GRs in ATP-depleted cells are associated with an RNAcontaining nuclear matrix. Quantitative Western blot (immunoblot) analysis confirmed the dramatic increase in GR binding to the nuclear matrix of ATP-depleted cells, while confocal microscopy revealed that GRs are bound to the matrix throughout all planes of the nucleus. ATP depletion does not lead to wholesale collapse of nuclear proteins onto the matrix, as the interaction of a subpopulation of simian virus 40 large tumor antigen with the nuclear matrix is not quantitatively altered in ATP-depleted Cos-1 cells. Nuclear GRs which are not bound to the nuclear matrix of metabolically active cells (i.e., a DNA-binding domain deletion mutant and a ␤-galactosidase chimera possessing the GR nuclear localization signal sequence) are not recruited to the matrix upon depletion of cellular ATP. Thus, it appears that ATP depletion does not expose the GR to nuclear matrix interactions which are not normally encountered in cells but merely alters the dynamics of such interactions. The dynamic association of steroid receptors with the nuclear matrix may provide a mechanism which is utilized by these regulable transcription factors to facilitate their efficient scanning of the genome.In recent years, there has been an increased appreciation for the extent to which distinct DNA, RNA, and protein components are organized within the nucleus (68). Much of the framework responsible for maintaining nuclear organization is provided for by the nuclear ...

show abstract

Nuclear architecture supports integration of physiological regulatory signals for transcription of cell growth and tissue‐specific genes during osteoblast differentiation

Cited by 43 publications

References 74 publications

The Matrix Attachment Region-Binding Protein SATB1 Participates in Negative Regulation of Tissue-Specific Gene Expression

The Matrix Attachment Region-Binding Protein SATB1 Participates in Negative Regulation of Tissue-Specific Gene Expression

The nuclear matrix protein NMP-1 is the transcription factor YY1.

ATP-Dependent Release of Glucocorticoid Receptors from the Nuclear Matrix

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