Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.21.1 (DNase)
7,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The principal regulator of erythropoiesis is the glycoprotein erythropoietin, which interacts with a specific cell surface receptor (EpoR). A study aimed at analyzing EpoR gene regulation has shown that both pluripotent embryonal stem cells and early multipotent hematopoietic cells express EpoR transcripts. Commitment to nonerythroid lineages (e.g., macrophage or lymphocytic) results in the shutdown of EpoR gene expression, whereas commitment to the erythroid lineage is concurrent with or followed by dramatic increases in EpoR transcription. To determine whether gene activity could be correlated with chromatin alterations, DNase-hypersensitive sites (HSS) were mapped. Two major HSS located in the promoter region and within the first intron of the EpoR gene are present in all embryonal stem and hematopoietic cells tested, the intensities of which correlate well with EpoR expression levels. In addition, a third major HSS also located within the first intron of the EpoR gene is uniquely present in erythroid cells that express high levels of EpoR. Transfection assays show that sequences surrounding this major HSS impart erythroid cell-specific enhancer activity to a heterologous promoter and that this activity is at least in part mediated by GATA-1. These data, together with concordant expression levels of GATA-1 and EpoR in both early multipotent hematopoietic and committed erythroid cells, support a regulatory role of the erythroid cell-specific transcription factor GATA-1 in EpoR transcription in these cells. However, the lack of significant levels of GATA-1 expression in embryonal stem cells implies an alternative regulatory mechanism of EpoR transcription in cells not committed to the hematopoietic lineage.
...
PMID:The gene for erythropoietin receptor is expressed in multipotential hematopoietic and embryonal stem cells: evidence for differentiation stage-specific regulation. 131 71

We identified the factor(s) that bind to the chicken erythroid-cell-specific histone H5 enhancer region which is located on the 3' end of the gene. In DNAase I footprinting and u.v. cross-linking experiments with nuclear extracts from adult chicken immature erythrocytes, we determined that the trans-acting factor GATA-1 was the predominating protein interacting with the histone H5 enhancer. GATA-2 and GATA-3 were not detected. In contrast, gel-mobility-shift assays and competition experiments demonstrated that several specific complexes formed with the histone H5 enhancer region. Gel-mobility-shift assays with 23 bp oligonucleotides containing the GATA-binding site (AGATAA) of the histone H5 enhancer or of the beta-globin enhancer showed that the GATA sequence was sufficient for the formation of at least five complexes. Diagonal mobility-shift assays demonstrated that multisubunit complexes were forming with the GATA-1 protein. Our interpretation of the results is that GATA-1 interacts with a protein of approx. 105 kDa which, in turn, can associate with protein or protein complexes of approx. 26 kDa, 146 kDa and a protein(s) of molecular mass greater than 450 kDa. The different multisubunit complexes formed via the trans-acting factor GATA-1 may impart different transcriptional responses to the promoter and enhancer elements of the histone H5 and globin genes.
...
PMID:Multisubunit erythroid complexes binding to the enhancer element of the chicken histone H5 gene. 159 Jul 78

The SCL/TAL-1 gene encodes a basic helix-loop-helix transcription factor that is expressed in multipotent hematopoietic progenitors before lineage commitment. Its expression is maintained during differentiation along erythroid, mast, and megakaryocytic lineages, but is repressed after commitment to nonexpressing lineages. To begin to address the molecular mechanisms underlying this complex pattern of expression, we have studied the regulation of the murine SCL promoter in erythroid and T-cell lines. Analysis of the methylation and chromatin structure of the SCL promoter region showed that SCL mRNA expression correlated with DNase hypersensitive sites and methylation status of the promoter. Transient reporter assays showed that promoter 1a was active in erythroid cells but not in T cells. Sequences between -187 and +26 were sufficient for lineage-restricted activity of promoter 1a. A joint promoter construct containing both promoter 1a and promoter 1b also exhibited lineage-restricted activity. Conserved GATA (-37), MAZ (+242), and ETS (+264) motifs were all shown to contribute to SCL promoter activity in erythroid cells, but several other motifs were not required for full promoter activity. The pattern of complexes binding to the +242 MAZ and +264 ETS sites were the same in erythroid and T cells. However, GATA-1 bound the -37 GATA site in erythroid cells, whereas in T cells GATA-3 was only able to bind weakly, if at all. Moreover, GATA-1 but not GATA-2 or GATA-3 was able to transactivate SCL promoter 1a in a T-cell environment. These results suggest that inactivity of SCL promoter 1a in T cells reflected the absence of GATA-1 rather than the presence of trans-dominant negative regulators.
...
PMID:Lineage-restricted regulation of the murine SCL/TAL-1 promoter. 763 58

We analyzed epsilon-globin transcription in erythroid cells and in erythroid extracts to determine the requirements for enhancer-dependent expression of this gene. Mutations that abolished GATA-1 binding at a single position in the promoter prevented interaction with enhancers, whereas elimination of a second more distal promoter GATA-1 site had no effect. Deletion or mutation of the GATA-1 sites in either the human beta-globin locus control region DNase-hypersensitive site II enhancer or the chicken beta A/epsilon-globin enhancer did not diminish the ability of the enhancers to interact with the promoter. In contrast, mutation of the AP-1/NF-E2 sites in these enhancers resulted in elimination of enhancement. In vitro transcription of these constructs was promoter dependent and was not sensitive to abolition of GATA-1 binding in the promoter, consistent with the role of GATA-1 solely as a mediator of the enhancer effect. Thus, GATA-1 regulates the response of the epsilon-globin gene to enhancers through a specific site in the promoter and requires enhancer AP-1/NF-E2 binding to transduce the enhancer effect on transcription.
...
PMID:Enhancer-dependent transcription of the epsilon-globin promoter requires promoter-bound GATA-1 and enhancer-bound AP-1/NF-E2. 842 10

In vitro DNAase I footprinting and gel mobility shift assays have shown that the activities of several nuclear factors (GATA-1, Sp1) that bind to the promoter and downstream enhancer regions of the chicken histone H5 gene are reduced in mature erythrocytes relative to those in immature erythrocytes. In this study we investigated site occupancy in the promoter and downstream enhancer regions of the H5 gene in mature and immature erythrocytes. The ligation-mediated polymerase chain reaction was used to detect DNAase I footprints generated in situ. Most of the sites that bound to Sp1 and/or Sp1-like proteins and GATA-1 in the promoter and enhancer were occupied in situ in mature and immature erythrocytes. However, the level of protection at Sp1/Sp-1-like binding sites in the H5 enhancer region of mature erythroid cells was generally less than that observed for immature cells, suggesting that for any given mature cell not all of the Sp1/Sp1-like binding sites are occupied. Nevertheless, the results of this study suggest that the enhancer and promoter of the H5 gene in mature erythrocytes should be functional, agreeing with nuclear run-on studies showing transcriptional activity of the H5 gene in mature permeabilized cells.
...
PMID:In situ footprinting of chicken histone H5 gene in mature and immature erythrocytes reveals common factor-binding sites. 862 38

Cis-acting elements of the gene for mouse glycophorin, an erythroid-specific membrane glycoprotein, were determined by transient and stable transfection assays using murine erythroleukemia (MEL) cells. Cis-acting elements proximal to the transcription start site of the gene can be separated into the basal promoter (-1 to 191 bp) and the distal element (-133 to -92). The basal promoter contained GGTGG and GATA motifs and the distal element contained GATA-1 and NF-E2 motifs. Deletion analysis of the distal GATA site and its neighboring sequence and DNase-I footprinting/EMSA (electrophoretic mobility shift assay) analysis indicated that induced nuclear factor binding to GATA-1 and its neighboring sequence may be required for expression during MEL cell differentiation induced by dimethyl sulfoxide treatment. The NF-E2 site was also shown to be essential for the promoter activity. An approximately 400 bp far upstream region (-1325 to -948bp) containing the binding motifs for GGGTGG, GATA-1 and NF-E2 showed no enhancing activity when this region was examined by transient transfection assay, but it did show enhancement of the differentiation-specific promoter activity in the stable transfection assay. The far upstream region of mouse glycophorin gene may have a function similar to that of the locus control region (LCR) of human beta-globulin gene cluster.
...
PMID:Inducible expression of erythroid-specific mouse glycophorin gene is regulated by proximal elements and locus control region-like sequence. 869 Jul 23

To study the mechanism of gene regulation for coagulation factor XIII A subunit (FXIIIA), we characterized its 5'-flanking region using a monocytoid (U937), a megakaryocytoid (MEG-01), and other cells. Our results confirmed that U937 and MEG-01 contained FXIIIA mRNA. A tentative transcription start site was determined to be 76 bases upstream from the first exon/intron boundary. Reporter gene assays revealed that a 5'-fragment (-2331 to +75) was sufficient to support basal expression in U937 and MEG-01 but not in the other cells. Deletion analysis confined a minimal promoter sequence from -114 to +75. DNase footprinting, electrophoretic mobility shift, and reporter gene assays demonstrated that promoter elements for a myeloid-enriched transcription factor (MZF-1-like protein) and two ubiquitous transcription factors (NF-1 and SP-1) in this region were important for the basal FXIII expression. It was also revealed that an upstream region (-806 to -290) had enhancer activity in MEG-01 but silencer activity in U937. DNA sequences for binding of myeloid-enriched factors (GATA-1 and Ets-1) were recognized in this region, and the GATA-1 element was found to be responsible for the enhancer activity. These transcription factors play a major role in the cell type-specific expression of FXIIIA, which differs from other transglutaminases.
...
PMID:Transcriptional regulation of cell type-specific expression of the TATA-less A subunit gene for human coagulation factor XIII. 1003 97

The chromatin structure of the human beta-globin gene locus assumes a transcriptionally-active conformation in erythroid cells. One feature of this chromatin reorganization is the formation of DNase 1 hypersensitive sites in the regions of active globin gene promoters. This reorganization requires the globin locus control region and is associated with normal expression of the beta-like globin genes. To determine whether it is possible to artificially enhance the opening of the chromatin structure of a minimal beta-globin promoter, we placed a 101bp, erythroid-specific DNase 1 hypersensitive site-forming element (HSFE) immediately upstream of the beta-globin promoter and gene. This element includes binding sites for NF-E2, AP-1, GATA-1 and Sp-1. Constructs were stably transfected into murine erythroleukemia cells and promoter chromatin structure and gene expression were analyzed. The HSFE induced an area of enhanced DNase 1 hypersensitivity extending from the transcriptional start site to -300bp of the artificial promoter and significantly increased the proportion of beta-globin promoters in an open chromatin configuration. This remodeling of promoter chromatin structure resulted in 3-fold increases in beta-globin gene transcription and induction, and inhibited long-term beta-globin gene silencing. These results indicate that a relatively small cis-acting element is able to enhance remodeling of promoter chromatin structure resulting in increased beta-globin gene expression.
...
PMID:Targeted remodeling of human beta-globin promoter chromatin structure produces increased expression and decreased silencing. 1034 13

Pax4 encodes a paired-box transcription factor and is essential for the differentiation of islet cells since the Pax4 homozygous mutant mice lack mature beta and delta cells. However, little is known about the transcriptional regulation of the Pax4 gene. We isolated and sequenced a 2.4-kb mouse genomic DNA fragment containing the 5' flanking sequence of Pax4 and identified a previously unrecognized intron. Primer extension revealed that this TATA-less promoter had only one transcription start site. The promoter activity of this fragment with various deletion mutants when tested in beta and non-beta cell lines indicated the presence of a beta-cell specific enhancer in the region, -1858 to -1954 bp. DNase 1 footprinting and gel retardation assays indicated that nuclear proteins from betaHC3 cells interacted with two sequences which contained putative CdxA/Nkx.2 and GATA-1,-2 binding sites. Site-directed mutagenesis indicated that both of these regions were necessary for beta-cell specific enhancer activity.
...
PMID:Cloning of the mouse Pax4 gene promoter and identification of a pancreatic beta cell specific enhancer. 1116 92

Upstream of the human epsilon-globin gene is the Locus Control Region (LCR) of the human beta-globin cluster, which consists of four DNase-I hypersensitive sites(HS1-HS4). It has been reported in transgenic experiments that HS3 preferentially regulates epsilon-globin gene expression. In order to elucidate the regulatory function of HS3 in the expression of globin gene, nuclear extracts from mouse hematopoietic tissues at several developmental stages were prepared and the binding of the nuclear factors to HS3 was analysed by using electrophoresis mobility shift assay(EMSA). Our results showed that the binding patterns of HS3 with nuclear extracts of mouse hematopoietic tissues at day 13 and day 18 of gestation were completely different; furthermore, by Southwestern Blot, the distinction between both stages was also demonstrated. It has been known that GATA and CACCC binding motifs are contained within HS3 core region. Using competitive gel-retardation assay, we found that no shift bands could be competed by using CACCC motif as a competitor. However one shift band at day 13 and day 18 of gestation could be competed respectively by using GATA motif as a competitor. We suggested that the shift bands, which could not be competed by both motifs, might be novel and stage-specific factors. In addition, by using Western Blot, we demonstrated that the two shift bands at day 13 and day 18 of gestation, competed by GATA motif, were GATA-2 and GATA-1 respectively: GATA-1 was expressed in mouse hematopoietic tissues at day 18 of gestation and not expressed at day 13 of gestation; however, GATA-2 was only expressed in mouse hematopoietic tissues at day 13 of gestation. According to these results, we speculated that HS3 might play an important role in regulation of stage-specific expression of globin genes through interaction between stage-specific nuclear factors and HS3.
...
PMID:[Studies on DNA-protein interactions in the HS3 of the human beta-LCR]. 1201 46


1 2 Next >>

---