Disease relevance of Hbb-b1

• Under these conditions the ratio of accumulated beta maj and beta min mRNA sequences approximates the 4:1 ratio observed in reticulocytes and murine erythroleukemia cells (MELC) induced to differentiate by hexamethylene bisacetamide (HMBA) [1].
• A 3.7-kilobase pair deletion including the entire beta major globin gene results in beta-thalassemia in a murine model of the disease (Skow, L. C., Burkhart, B. A., Johnson, F. M., Popp, R. A., Popp, D. M., Goldberg, S. Z., Anderson, W. F., Barnett, L. B., and Lewis, S. E. (1983) Cell 34, 1043-1052) [2].
• Mouse model of human beta zero thalassemia: targeted deletion of the mouse beta maj- and beta min-globin genes in embryonic stem cells [3].
• Transcription termination within the E1A gene of adenovirus induced by insertion of the mouse beta-major globin terminator element [4].
• The promoters examined were from the simian virus 40 early region, with or without its own 72-base-pair repeat, and the mouse beta major-globin gene [5].

High impact information on Hbb-b1

• SV40 recombinants carrying a functional RNA splice junction and polyadenylation site from the chromosomal mouse beta maj globin gene [6].
• A novel procedure for saturation mutagenesis of cloned DNA was used to obtain more than 100 single base substitutions within the promoter of the mouse beta-major globin gene [7].
• The third, cell-specific protein GT-IC exhibited a high affinity for both the GT-I motif and an upstream element in the promoter of the mouse beta-major-globin gene, suggesting that this protein can act both as an enhancer and an upstream element trans-acting factor [8].
• When the promoter regions from the mouse beta-maj globin or the human epsilon-globin genes are substituted for the viral promoter in the tk gene transformation occurs with 10-20% of the efficiency of the original plasmid [9].
• The possible regulatory role of DNA sequences situated 5' to the beta-maj globin gene was investigated by two types of assay [9].

Chemical compound and disease context of Hbb-b1

• Plasmid subclones of the 5' and 3' regions of the beta major-globin gene have been used as probes to assay the level and character of the transcripts of this gene in differentiating Friend erythroleukemia cells treated with dexamethasone [10].
• Finally, exposure to hypobaric hypoxia during midpregnancy led to increased maternal red blood cells, hemoglobin concentrations, hematocrit, and increased concentrations of maternal splenic mRNAs for key proteins involved in hemoglobin synthesis, erythroid Krüppel-like factor, erythroid 5-aminolevulinate synthase-2, and beta-major globin [11].

Biological context of Hbb-b1

• In Hbb-b1 cDNA, six base substitutions were found between the d and w1 haplotypes and also between p and w1, but none existed between d and p. In Hbb-b2 cDNA, three base substitutions were found between the d and w1 haplotypes and also between d and p, but none between p and w1 [12].
• Expression in the lens of 10 genes involved in apoptosis was also confirmed and, intriguingly, expression of hemoglobin isoforms (Hba-a1, Hba-X, Hbb-b1, Hbb-b2, and Hbb-Y) was confirmed using isotype specific primers [13].
• An N-ethyl-N-nitrosourea (ENU)-induced mutation in the Hbb-b1 gene of the mouse hemoglobin-beta complex (Hbb) has been shown to result in a high-oxygen affinity hemoglobin, homologous with hemoglobin Rainier in man (Peters, J., et al., Genetics 110:709, 1985) [14].
• A line of transgenic mice with two cointegrated transgenes, the human beta S- and alpha 2-globin genes, linked to the beta-globin locus control region was produced and bred with mice carrying a deletion of the mouse beta major-globin gene [15].
• A 3709 (+/- 2)-base pair (bp) region, including the entire beta major globin gene and 2 kilobases of 5' flanking region, is deleted [16].

Anatomical context of Hbb-b1

• We have analyzed the chromatin structure of the beta-major globin gene and other related beta-globin genes in induced and uninduced murine erythroleukemia (MEL) cell nuclei [17].
• The time of replication in S phase was determined for the 7.3 kb EcoRI segment containing the beta-major globin gene and the 14 kb EcoRI segment containing the beta-minor globin gene in a murine Friend erythroleukemia virus transformed (MEL) cell line [18].
• In the splenic erythroblasts, the chromatin structure in the vicinity of the beta-major globin gene was analyzed with two nucleases during these transcription rate changes [19].
• It is demonstrated that commitment and the actual expression of differentiation, as measured by the accumulation of alpha-, beta maj-, and beta min-globin mRNA, are temporally coordinated functions during induced differentiation of a transformed cell line by exposure to polar/apolar agents [20].
• RNA species have been identified in murine erythroid cells which contain both 5' flanking and structural gene sequences from the beta maj globin gene [21].

Associations of Hbb-b1 with chemical compounds

• Lines 745 and 707, from DBA/2 mice, produced 25%--48% beta-minor and 78%--52% beta-major globin following culture with DMSO [22].
• The results show that, during dimethyl sulfoxide-stimulated differentiation, transcription of alpha and beta major globin increases 15-25-fold, whereas beta minor globin transcription is not increased [23].
• The competence of Friend cells to express beta major globin genes is operated within 8 hours exposure to hexamethylenebisacetamide [24].
• The beta-major globin chains encoded by the two strains differ by three amino acids, one of which is a glycine-to-cysteine substitution at position 13 [25].
• In both cases, the decrease in methyl moieties occurs at a large number of CpG sites spread out over the entire genome, as indicated by a restriction enzyme analysis of several mouse genes including dhfr, beta-major globin, and the H-2K gene family [26].

Physical interactions of Hbb-b1

• Erythroid differentiation of mouse erythroleukemia cells results in reorganization of protein-DNA complexes in the mouse beta maj globin promoter but not its distal enhancer [27].
• EKLF was found to bind in vivo at both the mouse beta-major-globin promoter and the HS2 site of beta-LCR in the mouse erythroleukemia cells (MEL) in a DMSO-inducible manner [28].

Regulatory relationships of Hbb-b1

• Prolactin-like protein E (PLP-E) was recently found to stimulate expression of the adult beta major globin gene in mouse erythroleukemia cells [29].

Other interactions of Hbb-b1

• An extra band. distinct from the well-characterized globin chains (alpha, beta-maj, beta-min, beta-s), was detected in an adult erythrocyte sample of the C3H strain by urea triton polyacrylamide gel electrophoresis (UT-PAGE) analysis [30].
• Transcription of the erythroid-specific genes, alpha 1 and beta maj globin, is increased 10- to 30-fold, whereas synthesis of rRNA is suppressed, and there is activation or suppression of a number of additional genes that remain to be characterized [31].
• Analysis of the degree of Epo-dependent differentiation of the transfectants, based on the steady-state levels of beta major-globin mRNA, showed that the carboxyl terminal 133 amino acids and tyrosyl residues located at positions 429/431 and 460/464 were not necessary for the induction of differentiation [32].
• Spontaneous differentiation to the myeloid-macrophage, erythroid, or lymphoid pathway can be seen by morphologic criteria, detection of beta major globin synthesis, or expression of the early lymphoid specific transcription factor, Ikaros [33].
• Recombinant adenoviruses were constructed in which the viral E1A gene was deleted and the E1B promoter was replaced by the rat albumin, mouse beta-major globin, or mouse immunoglobulin heavy-chain promoter [34].

Analytical, diagnostic and therapeutic context of Hbb-b1

• Tissues from three transgenic mice mosaic due to the insertion of an exogenously introduced mouse beta-major globin gene were analyzed by genomic Southern-blotting and in situ hybridization [35].
• Lo by pronuclear injection of the cloned beta-major globin gene and comprises a highly reiterated sequence that is readily detected by DNA in situ hybridization on histological sections [36].
• Time course studies by Northern blot analysis demonstrated elevated levels of expression of beta-H1 and beta-Major globin genes in embryoid bodies derived from ES-hEpoR cells stimulated with Epo, when compared with similar expression from ES-Neo cells [37].
• Two nonpolyadenylated RNA transcripts, average 3700 and 1800-1900 nucleotides long, were identified by denaturing agarose gel electrophoresis and were found to hybridize to both 5' and 3' beta maj globin flanking sequences [21].
• DNA prepared from this material was amplified by the polymerase chain reaction (PCR), enabling identification of the normal beta-major globin gene in 11 out of 20 cases where it was known to be present [38].

References