Sequence-specific DNA-binding proteins are components of a nuclear matrix-attachment site.

Dworetzky, Steven I.; Wright, Kenneth L.; Fey, Edward G.; Penman, Sheldon; Lian, Jane B.; Stein, Janet L.

doi:10.1073/pnas.89.9.4178

Cited by 122 publications

(77 citation statements)

References 49 publications

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“…These ndings are in agreement with the increasing body of evidence demonstrating that different regulatory proteins are components of the nuclear matrix (22,(25)(26)(27)(28)(29)(30)(31)(32). The dynamic interactions of C/EBPa and PCNA with the nuclear matrix during liver development lend further support to the concept that the nuclear matrix facilitates gene expression by concentrating and localizing regulatory proteins near their target sites.…”

Section: Resultssupporting

confidence: 77%

The Protein Composition of the Hepatocyte Nuclear Matrix Is Differentiation‐Stage Specific

Ivanović‐Matić¹,

Dinić²,

Vujošević³

et al. 2000

IUBMB Life

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SummaryThe protein composition of hepatocyte nuclear matrices was examined in rats from the 16th day of gestation to 75 days after birth (adult). An overall increase in size of the nuclear matrix was accompanied by quantitative and qualitative changes in its protein content. Quantitative changes of the major proteins of the peripheral lamina surrounding the isolated nuclear matrix were detected. By Western analysis we established that in pre-and postnatal nuclear matrices the relative concentrations of lamin C were greater than lamin A. After birth, the relative concentrations of both lamins progressively increased. In the adult nuclear matrix, the concentration of lamin A was greater than lamin C. In contrast, the relative concentrations of lamin B remained unchanged throughout development and growth. The relative concentrations of two nuclear matrix -associated regulatory proteins studied changed with development and growth: transcription factor C/EBP® isoforms, which were detected during the gestation period, increased notably after the rst postnatal day, attaining a maximum at the adult stage; the high concentrations of the proliferating cell nuclear antigen (PCNA) perceptibly decreased after the 21st prenatal day. Changes in the composition of the nuclear matrix protein suggest that this structure coordinates nuclear functioning during cell differentiation.IUBMB Life, 49: 511 -517, 2000 Keywords C/EBPa ; hepatocyte development; lamins; nuclear matrix; PCNA.The nuclear matrix is a proteinaceous structural framework of the nucleus. The isolated matrix has a tripartite structure and

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Section: Resultssupporting

confidence: 77%

The Protein Composition of the Hepatocyte Nuclear Matrix Is Differentiation‐Stage Specific

Ivanović‐Matić¹,

Dinić²,

Vujošević³

et al. 2000

IUBMB Life

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“…These cells were proliferating just prior to the luciferase assay. Does the absence of somatic histone H1 in the two-cell mouse embryo imply that the AT tracts of the SAR sequences are unoccupied at this stage, or do histone H1 variants described in the early development of other species (19,47,56) (15,23,57). The presence of topoisomerase II consensus cleavage sequences in the SARs might also result in higher expression levels via introduction and/or maintenance of a level of torsional stress suitable for active transcription by RNA polymerase (11,26).…”

Section: Inspection Of the Results For Sar-lines Inmentioning

confidence: 99%

Scaffold attachment regions stimulate HSP70.1 expression in mouse preimplantation embryos but not in differentiated tissues.

Thompson¹,

Christians²,

Stinnakre³

et al. 1994

Mol. Cell. Biol.

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Eukaryotic interphase chromatin is thought to be organized into topologically discrete, independent domains acting as units upon which differential patterns of gene expression are established. Sequences which attach chromatin to in vitro preparations of a nucleoprotein matrix (scaffold attachment regions [SARs]) may act as domain boundaries, but their role remains poorly defined compared with those of other elements such as locus control regions. We have produced mice homozygous for a transgene which is transcribed as early as the activation of the embryonic genome at the two-cell stage and which is expressed ubiquitously in a number of differentiated tissues. Transgenic lines were generated in the presence or absence of flanking SAR sequences, creating an original model which enabled us to examine the effects of these elements at different developmental stages. In the preimplantation mouse embryo, flanking SARs stimulated transgene expression in a copydependent manner. In contrast, in the differentiated tissues of newborn and adult mice, no significant SAR-dependent increase in transgene expression was found, correlation with copy number was lost, and position effects were observed. These results suggest a limited capacity of SARs to act as insulating elements but are consistent with a proposed model of SAR-mediated chromatin opening and closing.There is increasing evidence that eukaryotic interphase chromatin is arranged on some form of structural skeleton which is thought to play roles in DNA transcription and replication (4,5,7,21,22,34,60). Thus, the eukaryotic genome seems to be divided into topologically constrained domains which may be involved in the organization of differential patterns of gene expression. The boundaries of these domains contain stretches of DNA which bind to in vitro preparations of the nuclear matrix or scaffold. These sequences, termed matrix. (11) (63) proposed an interesting model in which SARs might be involved in chromatin opening via interactions with nuclear proteins. That SAR elements are likely to be implicated in nuclear processes is also supported by the evolutionary conservation of these sequences from yeasts to humans (1,6,28,36,45,50

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“…Gene transcription that is both dependent on copy number and independent of chromosomal location can be conferred by the presence of MARs (34,83). Furthermore, actively transcribed genes appear to be associated with the nuclear matrix whereas transcriptionally inactive genes are not (32,38). In the case of the immunoglobulin heavy-chain locus, MARs flank the enhancer located between the joining and constant regions (19), and the intronic enhancer and flanking MARs are required for B-cell-specific expression of heavy chains (81).…”

mentioning

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

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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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Sequence-specific DNA-binding proteins are components of a nuclear matrix-attachment site.

Cited by 122 publications

References 49 publications

The Protein Composition of the Hepatocyte Nuclear Matrix Is Differentiation‐Stage Specific

The Protein Composition of the Hepatocyte Nuclear Matrix Is Differentiation‐Stage Specific

Scaffold attachment regions stimulate HSP70.1 expression in mouse preimplantation embryos but not in differentiated tissues.

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

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