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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecular genetic analysis of a number of vertebrate erythroid cell-specific genes has identified at least two types of cis-acting regulatory sequences which control the complex developmental pattern of gene expression during erythroid cell maturation. Tissue-specific cellular enhancers have been identified 3' to three erythroid cell-specific genes, and additional regulatory elements have been identified in the promoters of many erythroid genes. We show that the histone H5 enhancer, like the adult beta-globin enhancer, is involved in mediating the developmental induction of histone H5 mRNA as erythroid cells mature. We also describe the preliminary characterization of a tissue-specific regulatory element within the 5' region of the H5 locus and describe investigations of the interaction between this element and the histone H5 enhancer in mediating histone H5 regulation.
Mol Cell Biol 1989 May
PMID:Transcription of the chicken histone H5 gene is mediated by distinct tissue-specific elements within the promoter and the 3' enhancer. 274 49

An erythroid cell-specific nuclear factor that binds tightly to a sequence motif (5'-GATAAGGA-3') shared by many erythroid cell-specific promoters was purified to homogeneity by DNA sequence affinity chromatography. Visualization of the purified factor, which we term EF-1, showed a simple pattern comprising a polypeptide doublet with Mrs of 18,000 and 19,000. We confirmed that these species account for EF-1-binding activity by eluting the polypeptides from sodium dodecyl sulfate-polyacrylamide gels and renaturing the appropriate binding activity. Using the purified polypeptides, we mapped seven factor-binding sites that are dispersed across the murine alpha- and beta-globin genes. The murine alpha-globin gene is flanked by at least two EF-1-binding sites. One site is centered at nucleotide (nt) -180 (with respect to the alpha-globin cap site). A fivefold-weaker site is located downstream of the alpha-globin poly(A) addition site, at nt +1049. We mapped five EF-1-binding sites near the murine beta-globin gene. The strongest site was centered at nt -210. Four additional sites were centered at nt -266 (adjacent to the binding site of a factor present in both murine erythroleukemia and Raji cells), -75 (overlapping the beta-globin CCAAT box), +543 (within the second intervening sequence), and -111.
Mol Cell Biol 1989 Jun
PMID:Purification and characterization of an erythroid cell-specific factor that binds the murine alpha- and beta-globin genes. 276 41

Nondefective Friend murine leukemia virus (MuLV) causes erythroleukemia when injected into newborn NFS mice, while Moloney MuLV causes T-cell lymphoma. Exchange of the Friend virus enhancer region, a sequence of about 180 nucleotides including the direct repeat and a short 3'-adjacent segment, for the corresponding region in Moloney MuLV confers the ability to cause erythroid disease on Moloney MuLV. We have used the electrophoretic mobility shift assay and methylation interference analysis to identify cellular factors which bind to the Friend virus enhancer region and compared these with factors, previously identified, that bind to the Moloney virus direct repeat (N. A. Speck and D. Baltimore, Mol. Cell. Biol. 7:1101-1110, 1987). We identified five binding sites for sequence-specific DNA-binding proteins in the Friend virus enhancer region. While some binding sites are present in both the Moloney and Friend virus enhancers, both viruses contain unique sites not present in the other. Although none of the factors identified in this report which bind to these unique sites are present exclusively in T cells or erythroid cells, they bind to three regions of the enhancer shown by genetic analysis to encode disease specificity and thus are candidates to mediate the tissue-specific expression and distinct disease specificities encoded by these virus enhancer elements.
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PMID:Nuclear factors that bind to the enhancer region of nondefective Friend murine leukemia virus. 277 72

Chicken erythroid cells at different stages of maturation were incubated with [14C]tyrosine to analyze the incorporation of this amino acid into the COOH-terminus of alpha-tubulin. The incorporated radioactivity was determined in the microtubule and nonassembled tubulin pools. At all maturation stages, nonassembled tubulin was more labeled than microtubules. Microtubules were significantly labeled in proerythroblasts, labeled to a lesser extent in erythroblasts and not labeled at all in mature erythrocytes. We also studied the distribution of the tyrosinating and detyrosinating enzymes, tubulin:tyrosine ligase and tubulin carboxypeptidase, respectively, between the assembled and nonassembled tubulin fractions. Tubulin:tyrosine ligase behaved as a soluble entity at all maturation stages, whereas tubulin carboxypeptidase was found partially associated with microtubules in chicken proerythroblasts and completely soluble in mature erythrocytes. The marginal band of toad erythrocytes was examined by immunofluorescence using antibodies specific to tyrosinated and to detyrosinated tubulin. This marginal band which is mainly tyrosinated could be detyrosinated by exposure of these cells, previously permeabilized, to exogenously supplied tubulin carboxypeptidase. Toad erythrocytes contained soluble tubulin carboxypeptidase which showed an activity similar to that of chicken erythrocytes.
Mol Cell Biochem 1989 Aug 15
PMID:Tyrosination-detyrosination of tubulin and microtubules during the development of chick erythrocytes. 277 46

Hemin-induced differentiation of the human erythroleukemia cell line K562 results in the expression and accumulation of erythroid-specific gene products such as embryonic and fetal hemoglobins and the elevated synthesis of the major heat shock protein HSP70. This activity was suggested to represent activation of a heat shock gene during erythroid maturation independent of stress induction. In this study, we demonstrate that hemin induces the transcription of two members of the human HSP70 gene family, HSP70 and GRP78 (BiP). However, the induction of HSP70 by hemin showed characteristics consistent with the molecular events associated with a heat shock or stress response. The increase in HSP70 gene transcription was accompanied by induction of the stress-induced form of the heat shock transcription factor. Moreover, a heat shock element was required for the hemin responsiveness of chimeric heat shock promoter-chloramphenicol acetyltransferase genes transiently expressed in transfected K562 cells.
Mol Cell Biol 1989 Aug
PMID:Hemin-induced transcriptional activation of the HSP70 gene during erythroid maturation in K562 cells is due to a heat shock factor-mediated stress response. 279 86

Using a restriction enzyme accessibility assay, we have previously demonstrated that the chromatin structure immediately proximal to the goat beta F-, beta C-, and beta A-globin genes changes in a manner which parallels their developmentally regulated expression. More specifically, the PvuII recognition sequence, located 9 nucleotides upstream from the transcriptional start site in each of the three genes, is accessible to digestion only in nuclei prepared from erythroid tissue in which the respective gene product is expressed. Here we describe two restriction enzyme sites further upstream from the transcription start sites (HindIII at -700 and SacI at -480) which were not accessible to digestion in fetal erythroid nuclei. Conversely, two sites within the second coding block of the beta F gene (AccI at +276 and BamHI at +470) were accessible in fetal erythroid tissue. The corresponding sites in the beta C and beta A genes were not available for digestion in the same fetal tissue. Processive exonuclease III digestion in situ from the three accessible restriction enzyme sites in the beta F gene allowed us to define more closely the limits of these open regions. Resistance to exonuclease III digestion was encountered at or near both intron-exon junctions flanking the first intervening sequence of the beta F gene. Conversely, no resistance to exonuclease III digestion was evident in either the first or second coding blocks or the 5' untranslated region. Digestion upstream from the PvuII site of the beta F gene was negligible. High-resolution mapping by S1 nuclease analysis indicated that the endpoint of exonuclease III digestion from this site lay immediately downstream of the ATA box.
Mol Cell Biol 1987 Aug
PMID:Chromatin fine-structure mapping of the goat beta F gene in fetal erythroid tissue. 282 4

The human G gamma-globin and beta-globin genes are expressed in erythroid cells at different stages of human development, and previous studies have shown that the two cloned genes are also expressed in a differential stage-specific manner in transgenic mice. The G gamma-globin gene is expressed only in murine embryonic erythroid cells, while the beta-globin gene is active only at the fetal and adult stages. In this study, we analyzed transgenic mice carrying a series of hybrid genes in which different upstream, intragenic, or downstream sequences were contributed by the beta-globin or G gamma-globin gene. We found that hybrid 5'G gamma/3'beta globin genes containing G gamma-globin sequences upstream from the initiation codon were expressed in embryonic erythroid cells at levels similar to those of an intact G gamma-globin transgene. In contrast, beta-globin upstream sequences were insufficient for expression of 5'beta/3'G gamma hybrid globin genes or a beta-globin-metallothionein fusion gene in adult erythroid cells. However, beta-globin downstream sequences, including 212 base pairs of exon III and 1,900 base pairs of 3'-flanking DNA, were able to activate a 5'G gamma/3'beta hybrid globin gene in fetal and adult erythroid cells. These experiments suggest that positive regulatory elements upstream from the G gamma-globin and downstream from the beta-globin gene are involved in the differential expression of the two genes during development.
Mol Cell Biol 1987 Nov
PMID:Upstream G gamma-globin and downstream beta-globin sequences required for stage-specific expression in transgenic mice. 282 25

A full-length human c-myb cDNA clone has been isolated from a CCRF-CEM leukemia cell cDNA library. The plasmid vector contains simian virus 40-derived promotor, splice, and polyadenylation sequences as well as a transcription unit for a dihydrofolate reductase cDNA. We have introduced this construct into Friend erythroleukemia (F-MEL) cells and have isolated a number of clones which contain intact and transcriptionally active human c-myb sequences. F-MEL clones expressing the highest levels of the human c-myb mRNA differentiate poorly in response to dimethyl sulfoxide. Two clones which initially expressed low levels of human c-myb transcripts and which differentiated normally were subsequently inhibited in their ability to differentiate when grown in successively higher concentrations of methotrexate, due to amplification and enhanced expression of plasmid sequences. The inhibitory effect on F-MEL differentiation appeared to be independent of the early decline in c-myc transcripts which were normally regulated in all cases examined. Our results indicate that constitutive expression of a nontruncated human c-myb cDNA can exert profound effects on erythroid differentiation and argue for a causal role of c-myb in the F-MEL differentiation process.
Mol Cell Biol 1988 Feb
PMID:Constitutive expression of a c-myb cDNA blocks Friend murine erythroleukemia cell differentiation. 283 42

Isolation and characterization of the chicken erythroid anion transporter (band 3) cDNA clone, pCHB3-1, revealed that the chicken erythroid band 3 polypeptide is 844 amino acids in length with a predicted mass of 109,000 daltons. This polypeptide is composed of a hydrophilic N-terminal cytoplasmic domain and a hydrophobic C-terminal transmembrane domain. The approximately 90 N-terminal amino acids of the human and murine erythroid band 3 polypeptides are absent in the predicted sequence of the chicken erythroid band 3 polypeptide. The absence of this very acidic N-terminal region is consistent with the lack of binding of glyceraldehyde-3-phosphate dehydrogenase to chicken erythroid band 3, as well as the relatively basic isoelectric point observed for this molecule. The remainder of the cytoplasmic domain shows little similarity to the cytoplasmic domain of the murine and human erythroid band 3, with the exception of the putative ankyrin-binding site, which is highly conserved. In contrast, the transmembrane domain of the chicken band 3 polypeptide is very similar to that of the murine erythroid and human nonerythroid band 3 polypeptides. The transmembrane domain contains 10 hydrophobic regions that could potentially traverse the membrane 12 to 14 times. In addition, a variant of chicken erythroid band 3, pCHB3-2, was cloned in which one of the hydrophobic regions of pCHB3-1 is lacking. The transcript complementary to pCHB3-2 accumulated in chicken erythroid cells in a similar manner as the transcript complementary to pCHB3-1 during embryonic development. This is the first example of a transporter protein or ion channel with alternative primary structures in its membrane-spanning segments.
Mol Cell Biol 1988 Mar
PMID:Alternative primary structures in the transmembrane domain of the chicken erythroid anion transporter. 283 70

The avian erythroblastosis virus v-erbA locus potentiates the oncogenic transformation of erythroid and fibroblast cells and is derived from a host cell gene encoding a thyroid hormone receptor. We report here the use of site-directed mutagenesis to identify and characterize functional domains within the v-erbA protein. Genetic lesions introduced into a putative hinge region or at the extreme C-terminus of the v-erbA coding domain had no significant effect on the biological activity of this polypeptide. In contrast, mutations introduced within the cysteine-lysine-arginine-rich center of the v-erbA coding region, a DNA-binding domain in the thyroid and steroid hormone receptors, abolished or severely compromised the ability of the viral protein to function. Our results suggest that the mechanism of action of the v-erbA protein in establishing the neoplastic phenotype is closely related to its ability to interact with DNA, presumably thereby altering expression of host target genes by either mimicking or interfering with the action of the normal c-erbA gene product.
Mol Cell Biol 1988 Oct
PMID:Genetic dissection of functional domains within the avian erythroblastosis virus v-erbA oncogene. 284 34


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