The sequence-specific nuclear matrix binding factor F6 is a chicken GATA-like protein

Vassetzky, Yegor S.; Gallo, C.; Bogdanova, A. N.; Razin, Sergey V.; Scherrer, Klaus

doi:10.1007/bf00291988

Cited by 18 publications

(12 citation statements)

References 32 publications

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“…The importance of MARs in tissue-and cell-type-specific gene expression has been established in model transfection studies and in transgenic animals (71,82). 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).…”

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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 ...

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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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“…From a DNase I-hypersensitive site 14.5 kb upstream of the ir-,aD-, and aA-globin genes (8, 9) to a hypersensitive site 3 kb downstream of the gene cluster, multiple DNA elements such as matrix attachment regions (MARs) (8, 10, 11), topoisomerase II sites (6,8,12), a replication origin (13), enhancers (14-18), and a silencer (17) all thought to represent putative control elements, have been identified, in addition to the promoters of the individual genes (19,20) and repetitive DNA sequences (21). This region seems to be transcribed into a full-domain transcript which spans the entire domain between the most distal DNase I-hypersensitive sites (8,22,23), running right through all the DNA in the area between the external MARs, and also through an internal MAR placed upstream of the first gene.For the present investigation it was important that the positions of MARs (8,10) and topoisomerase II cleavage sites (24) had been mapped in this area and that multiple sites of protein-DNA interaction were identified within the 1.7-kb fragment including the putative origin of replication (13) and a replication-related MAR (10,11,25). We found that nuclease Sl-sensitive regions are located both upstream and downstream of the domain and that, in the upstream area, they coincided with the permanent site of DNA attachment to the nuclear matrix.…”

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confidence: 99%

“…This domain represents one of the best studied genomic areas in higher eukaryotes in terms of the arrangement of up to 35 kb of DNA elements involved in chromatin structure, mechanisms of transcription, and control of gene expression. From a DNase I-hypersensitive site 14.5 kb upstream of the ir-,aD-, and aA-globin genes (8,9) to a hypersensitive site 3 kb downstream of the gene cluster, multiple DNA elements such as matrix attachment regions (MARs) (8,10,11), topoisomerase II sites (6,8,12), a replication origin (13), enhancers (14)(15)(16)(17)(18), and a silencer (17) all thought to represent putative control elements, have been identified, in addition to the promoters of the individual genes (19,20) and repetitive DNA sequences (21). This region seems to be transcribed into a full-domain transcript which spans the entire domain between the most distal DNase I-hypersensitive sites (8,22,23), running right through all the DNA in the area between the external MARs, and also through an internal MAR placed upstream of the first gene.…”

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confidence: 99%

Excision close to matrix attachment regions of the entire chicken alpha-globin gene domain by nuclease S1 and characterization of the framing structures.

Targa

Razin

Gallo

et al. 1994

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

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Nuclease Sl-hypersensitive sites in a 40-kb region of the chicken genome including the domain of the a-globin genes were mapped. Brief treatment of isolated chicken erythroid cell nudei with nuclease SI allowed separation ofan %20-kb genomic DNA fragment containing the whole a-globin gene duster. No Sl-hypersensitive sites were observed in the internal part of the domain. The upstream SI site was found in a DNA fragment of 1.7 kb where the origin of replication and several protein binding sites were identified previously. Precise mapping of the positions of SI cleavage in this fragment and "in vivo" footprinting of DNA-protein interactions in isolated nuclei showed a correspondence with some of these protein binding sites. The possible signfcance of all these observations is di in connection with the replication origin and the nuclear matrix attachment regions in the aming structures.In the nuclei of eukaryotic cells, the DNA is organized into large loops fixed to the nuclear skeleton (1-5). The specificity of loop organization-i.e., the specificity of distribution of the loop borders in the genome-has been intensively studied but the experimental results remain controversial (1,4 To investigate loop organization, we have now mapped, in interphase nuclei of erythroid cells, sites of preferential S1 cleavage within the chicken DNA fragment containing the domain of the a-globin genes. This domain represents one of the best studied genomic areas in higher eukaryotes in terms of the arrangement of up to 35 kb of DNA elements involved in chromatin structure, mechanisms of transcription, and control of gene expression. From a DNase I-hypersensitive site 14.5 kb upstream of the ir-,aD-, and aA-globin genes (8, 9) to a hypersensitive site 3 kb downstream of the gene cluster, multiple DNA elements such as matrix attachment regions (MARs) (8, 10, 11), topoisomerase II sites (6,8,12), a replication origin (13), enhancers (14-18), and a silencer (17) all thought to represent putative control elements, have been identified, in addition to the promoters of the individual genes (19,20) and repetitive DNA sequences (21). This region seems to be transcribed into a full-domain transcript which spans the entire domain between the most distal DNase I-hypersensitive sites (8,22,23), running right through all the DNA in the area between the external MARs, and also through an internal MAR placed upstream of the first gene.For the present investigation it was important that the positions of MARs (8,10) and topoisomerase II cleavage sites (24) had been mapped in this area and that multiple sites of protein-DNA interaction were identified within the 1.7-kb fragment including the putative origin of replication (13) and a replication-related MAR (10,11,25). We found that nuclease Sl-sensitive regions are located both upstream and downstream of the domain and that, in the upstream area, they coincided with the permanent site of DNA attachment to the nuclear matrix. In the upstream area, the exact positions of S1 cleavage and DNA-pro...

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“…1C. Several proteins that specifically bind to ARSc, MAR, and SAR DNA have been identified (14,16,18,26,34,45). The similarity of the AT-rich FVIII cDNA sequences to MAR and SAR DNA and the ARSc suggested that the ARSc-and MAR-like sequences in the FVIII cDNA might interact with cellular fac- tors.…”

Section: Resultsmentioning

confidence: 99%

The Human Clotting Factor VIII cDNA Contains an Autonomously Replicating Sequence Consensus- and Matrix Attachment Region-Like Sequence That Binds a Nuclear Factor, Represses Heterologous Gene Expression, and Mediates the Transcriptional Effects of Sodium Butyrate

Fallaux

Hoeben

Cramer

et al. 1996

Molecular and Cellular Biology

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Expression of the human blood-clotting factor VIII (FVIIIHemophilia A is a bleeding disorder that affects approximately 1 in 10,000 males and is caused by a deficiency of functional blood coagulation factor VIII (FVIII). Protein replacement therapy has been effective and has resulted in both a dramatic increase in life expectancy and a vast improvement in the quality of life (41). However, therapy with plasma-derived FVIII has resulted in transmission of several human viruses, such as human immunodeficiency virus and hepatitis viruses (39). The ideal therapy, therefore, would be independent of blood-derived products. The recent use of recombinant-DNA-derived FVIII for treatment of hemophilia A (35) is a major step in that direction, but extensive use of this product is still problematic because of the high cost of recombinant FVIII. Therefore, somatic gene therapy is an appealing alternative for hemophilia treatment (15,24,42).As a first step in this direction, gene therapists have focused on the development of retroviral vectors and ex vivo strategies for the transfer and expression of the human blood-clotting FVIII cDNA. It has been shown previously that the FVIII proteins secreted by various cell types are fully functional (25,27). However, the titers of the retroviruses carrying the FVIII cDNA (Ͻ10 4 CFU/ml) are much lower than those routinely obtained with vectors that carry other genes (Ͼ10 6 CFU/ml), and the amounts of protein that infected cells secrete are smaller (22,24,25,27,32,36).Several causes have been named to explain the low level of FVIII expression, such as inefficient intracellular transport of FVIII, inefficient FVIII secretion, and extreme susceptibility of this clotting factor to proteolytic degradation (11,12,29,30,40). In addition, reduced FVIII mRNA accumulation has been observed in various cell types, like Swiss 3T3, primary human skin fibroblasts, Rat2 fibroblasts, and Chinese hamster ovary (CHO)-derived cell lines (22,30,36). Interestingly, treatment of CHO-derived cell lines and Rat2 fibroblasts with sodium butyrate raised their steady-state FVIII mRNA and protein levels (11,22,29). The mechanism by which butyrate exerts this effect is still unclear.Lynch and coworkers (36) demonstrated that inhibition of FVIII mRNA accumulation in retrovirus-packaging and trans-* Corresponding author. Mailing address:

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The sequence-specific nuclear matrix binding factor F6 is a chicken GATA-like protein

Cited by 18 publications

References 32 publications

ATP-Dependent Release of Glucocorticoid Receptors from the Nuclear Matrix

ATP-Dependent Release of Glucocorticoid Receptors from the Nuclear Matrix

Excision close to matrix attachment regions of the entire chicken alpha-globin gene domain by nuclease S1 and characterization of the framing structures.

The Human Clotting Factor VIII cDNA Contains an Autonomously Replicating Sequence Consensus- and Matrix Attachment Region-Like Sequence That Binds a Nuclear Factor, Represses Heterologous Gene Expression, and Mediates the Transcriptional Effects of Sodium Butyrate

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