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

The beta-globin haplotypes of 852 chromosomes from 12 populations in the Asia-Pacific region are described. These data are combined with those from other populations in an investigation of the affinities of regional human populations. Both partial maximum-likelihood and distance Wagner methods indicate that Africans are the most divergent group, with the remaining populations branching in the following order: Australian Aborigines, Highland Melanesians, Lowland Melanesians, Indonesians and Micronesians, Polynesians, east Asians, Indians, and Europeans. This pattern of relationship is consistent with that indicated by other data. Analysis of the evolution and distribution of haplotype occurrence provides some limited support for an origin of modern humans in Africa. Otherwise, however, it was not useful in further elucidating the evolutionary history of human populations.
Mol Biol Evol 1990 Sep
PMID:Evolution of beta-globin haplotypes in human populations. 197 32

The role of RNA sequences in the 5' leader region between the cap site and initiating AUG in mediating translation was examined in vitro. Hybrid mRNAs were synthesized in which the cognate leader sequence was replaced with either optimized or compromised leader sequences, and translational efficiency was measured for six different coding regions. Translation was most efficient with a leader containing the 5' untranslated region from Xenopus beta-globin and an optimized initiation sequence. Compared with the cognate leaders, this hybrid was observed to increase translation of the various coding regions as much as 300-fold. The translational efficiencies of the different coding regions also varied substantially. In contrast to earlier suggestions that increased leader efficiency results from higher affinity of the leader for a limiting factor, our experiments suggest that increased translation from the beta-globin hybrid leader sequence results from more rapid initiation of translation.
Mol Cell Biol 1991 May
PMID:Both the 5' untranslated region and the sequences surrounding the start site contribute to efficient initiation of translation in vitro. 201 71

We have expressed human alpha-globin to a high level in Escherichia coli as a fusion protein, purified it and removed the N-terminal leader sequence by site-specific proteolysis with blood coagulation factor Xa. The apo globin has been refolded and reconstituted with haem and native beta-globin to form fully functional haemoglobin (Hb) with properties identical to those of native human Hb. By site-directed mutagenesis we have altered the distal residues of the alpha subunits and compared the functional properties of these mutant proteins. The rates of various ligands binding to these proteins in the R-state have been reported by Mathews et al. Here, we present the oxygen equilibrium curves of three E11 alpha mutants and the crystal structures of two of these mutants in the deoxy form. Replacing the distal valine residue of alpha-globin with alanine, leucine or isoleucine has no effect on the oxygen affinity of the protein in either quaternary state, in contrast to the equivalent mutations of beta subunits. The crystal structure of the valine E11 alpha----isoleucine mutant shows that the larger E11 residue excludes water from the haem pocket, but causes no significant movement of other amino acid residues. We conclude that the distal valine residue of alpha-globin does not control the oxygen affinity of the protein by sterically hindering ligand binding.
J Mol Biol 1991 Apr 20
PMID:Functional role of the distal valine (E11) residue of alpha subunits in human haemoglobin. 202 47

Steroid receptors have been reported to stimulate transcription in a manner synergistic with other transcription factors. We have examined this synergism or functional cooperativity between glucocorticoid receptors and basal transcription factors in a variety of promoter and reporter gene contexts. A fragment containing a hormone response element from mouse mammary tumor virus was fused to well characterized promoters from the herpes virus thymidine kinase and mouse beta-globin genes and to related mutant promoters altered by inactivation of transcription factor-binding sites through point mutagenesis or deletion. These constructs were transfected into glucocorticoid-sensitive fibroblasts, and reporter gene activity was assessed with or without hormonal stimulation. In contrast to previous studies, we found little indication of synergistic interaction between elements mediating a hormone response and adjacent basal promoters. In fact, we observed that inactivating basal factor-binding sites, thereby decreasing promoter strength, actually increased hormone inducibility. We suggest that the inverse relationship between basal promoter strength and the induction ratio attained upon hormonal stimulation may be due to limitation of a common factor, an "adaptor" through which glucocorticoid receptor and basal transcription factors interact with the components of the RNA polymerase II complex to stimulate rates of transcription.
Mol Endocrinol 1991 May
PMID:Concerted stimulation of transcription by glucocorticoid receptors and basal transcription factors: limited transcriptional synergism suggests mediation by coactivators/adaptors. 207 21

A point mutation G-A in the 110 position of the beta-globin gene small intron has been revealed by cloning and sequencing from the material of a homozygote beta-thalassemia patient in Azerbaijan. In the present study two allele-specific oligonucleotide probes for testing the mutation have been synthesized. Assessment frequency of the mutation among the beta-thalassemia patients in Azerbaijan has been performed with the use of the amplified beta-globin gene fragments obtained by using the thermostable DNA-polymerase from T. thermophilus with the subsequent dot-hybridization in gel of the amplified material with the oligonucleotide probes. The possibility to test the mutation by hybridization of the oligonucleotide probes with the donors and beta-thalassemia patients restricted genomic DNA has been analyzed. Only one of 50 thalassemia alleles of beta-globin genes under study has been shown to possess the mutation mentioned.
Mol Gen Mikrobiol Virusol 1990 Jan
PMID:[Testing of G----A mutation in position 110 of a minor intron of beta-globin genes in patients with thalassemia in Azerbaijan]. 213 13

We have mapped DNase I-hypersensitive sites and topoisomerase II (topo II) sites in the chicken beta-globin locus, which contains four globin genes (5'-rho-beta H-beta A-epsilon-3'). In the 65 kilobases (kb) mapped, 12 strong hypersensitive sites were found clustered within the 25-kb region from 10 kb upstream of rho to just downstream of epsilon. The strong sites were grouped into several classes based on their tissue distribution, developmental pattern, and location. (i) One site was present in all cells examined, both erythroid and nonerythroid. (ii) Three sites, located upstream of the rho-globin gene, were present at every stage of erythroid development, but were absent from nonerythroid cells. (iii) Four sites at the 5' ends of each of the four globin genes were hypersensitive only in the subset of erythroid cells that were transcribing or had recently transcribed the associated gene. (iv) Another three sites, whose pattern of hypersensitivity also correlated with expression of the associated gene, were found 3' of rho, beta H, and epsilon. (v) A site 3' of beta A and 5' of epsilon was erythroid cell specific and present at all developmental stages, presumably reflecting the activity of this enhancer throughout erythroid development. We also mapped the topo II sites in this locus, as determined by teniposide-induced DNA cleavage. All strong teniposide-induced cleavages occurred at DNase I-hypersensitive sites, while lesser amounts of cleavage were observed in transcribed regions of DNA. Most but not all of the DNase I-hypersensitive sites were topo II sites. These data are consistent with the hypothesis that, in vivo, topo II preferentially acts on nucleosome-free regions of DNA but suggest that additional topo II regulatory mechanisms must exist.
Mol Cell Biol 1990 Jun
PMID:Developmental regulation of topoisomerase II sites and DNase I-hypersensitive sites in the chicken beta-globin locus. 216 May 85

Enhancers stimulate transcription of RNA polymerase II-transcribed genes in an orientation-independent manner and over long distances. This stimulation is known to be associated with an increased polymerase density over the linked gene. However, many aspects of the exact mechanism of remote gene control remain to be elucidated. Based on some reports on RNA polymerase I transcription, we wanted to test whether RNA polymerase II enters at the enhancer and from there proceeds towards the promoter while synthesizing unstable transcripts ("scanning/readthrough transcription" model). For this, we have inserted a complete terminator region from the mouse beta-globinmaj gene between the SV40 enhancer and the rabbit beta-globin promoter. In contrast to what the model predicts, insertion of the terminator had no affect on remote enhancer action. Furthermore, we have determined the RNA polymerase density over the spacer DNA between enhancer and promoter, and over the reporter gene, by means of the so-called run-on transcription assay. We find very low transcription of the spacer, but high transcription of the globin reporter gene. Thus, our data are not consistent with a scanning/readthrough transcription mechanism where RNA polymerase II would move from the enhancer to the promoter while transcribing the intervening spacer DNA. These and other findings are compatible with a model where enhancer and promoter are brought into close proximity, perhaps with concomitant looping out of the intervening DNA.
Somat Cell Mol Genet 1990 Jul
PMID:A transcriptional terminator between enhancer and promoter does not affect remote transcriptional control. 221 23

The functional organization of the rat brain creatine kinase (ckb) promoter was analyzed by deletion, linker scanning, and substitution mutagenesis. Mutations were introduced into the ckb promoter of hybrid ckb/neo (neomycin resistance gene) genes, and the mutant genes were expressed transiently in HeLa cells. Expression was assayed by primer extension analysis of neo RNA, which allowed the transcription start sites and the amount of transcription to be determined. Transfections and primer extension reactions were internally controlled by simultaneous analysis of transcription from the adenovirus VA gene located on the same plasmid as the hybrid ckb/neo gene. We demonstrate that 195 bp of the ckb promoter is sufficient for efficient in vivo expression in HeLa cells. A nonconsensus TTAA element at -28 bp appears to provide the TATA box function for the ckb promoter in vivo. Two CCAAT elements, one at -84 bp and the other at -54 bp, and a TATAAA TA element (a consensus TATA box sequence) at -66 bp are required for efficient transcription from the TTAA element. In addition, we present evidence that the consensus beta-globin TATA box responds to the TATAAATA element in the same way as the ckb nonconsensus TTAA element.
Mol Cell Biol 1990 Dec
PMID:Identification of cis-acting regulatory elements in the promoter region of the rat brain creatine kinase gene. 224 71

We have reported in rat three adult beta-gene haplotypes containing either five or three genes. Detailed sequence analysis reveals that the leftmost gene is the major gene and that at the opposite end downstream lies the minor gene. All of the genes lying between them are minor-major hybrids indicating their origin by unequal crossing-over. In two haplotypes beta-globin genes were found with an L1(1) element inserted directly into IVS2. The described results allow the formulation of a pathway of mutational events leading from the ancient two-beta-gene rodent ancestor through a three-gene haplotype to five-gene haplotypes, one of which is postulated to have arisen in common laboratory strains since their capture in the wild.
Mol Biol Evol 1990 Sep
PMID:Origin of rat beta-globin haplotypes containing three and five genes. 226 93

The relationship between preferences among alternative 5' splice sites and their sequences has been investigated for 37 sequences by assessing their use in splicing relative to the 5' splice site of IVS-2 of rabbit beta-globin. There are strong correlations between the intrinsic strength of a 5' splice site and both the extent to which it resembles the consensus sequence and the calculated stability of its interactions with U1 small nuclear RNA. However, present methods of calculating either of the latter values do not allow predictions to be made of the relative preferences among a small number of sequences.
J Mol Biol 1990 Jan 05
PMID:Hierarchy for 5' splice site preference determined in vivo. 229 64


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