Disease relevance of VEZF1

• We describe the isolation of two recombinant lambda phages, each containing genomic DNA fragments encoding both the major adult alpha- and beta-globin mRNAs of X. laevis [1].
• Hemin increased beta globin synthesis two- to threefold in chick erythrocyte-NA neuroblastoma heterokaryons; however, total globin synthesis was still less than 10% that of L6 heterokaryons [2].
• Specific factor conferring nuclease hypersensitivity at the 5' end of the chicken adult beta-globin gene [3].
• To overcome this problem, we investigated whether the HS4 chromatin insulator from the chicken beta-globin locus control region could protect a retrovirus vector from position effects [4].
• To test the appropriate expression and inducibility of chicken globin genes in murine erythroleukemia (MEL) cells, an adult chicken beta-globin gene construct was stably transfected [5].

High impact information on VEZF1

• We have identified a 42 bp fragment of the chicken beta-globin insulator that is both necessary and sufficient for enhancer blocking activity in human cells [6].
• A 5' element of the chicken beta-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila [7].
• In this paper we show that the beta-globin enhancer stimulates transcription of both genes. epsilon-Globin is, however, inappropriately regulated since it is expressed in both embryonic and adult red blood cells [8].
• We have studied the properties of a factor or factors that bind selectively to the 5' flanking region of the chicken adult beta-globin (beta A-globin) gene [9].
• Comparison with the sequences of the chicken rho-globin and beta-globin genes reveals the presence of two regions that are identical or nearly identical in epsilon and rho [10].

Biological context of VEZF1

• Although both BGP1 and Sp1 require Zn2+ for their DNA-binding activity, these proteins differ in their binding-site specificities, chromatographic properties, and molecular weights [11].
• The minimal binding sequence is seven dG residues; methylation interference studies show that each of these residues contacts BGP1 [12].
• Electron microscopic visualization of R loop structures generated by hybridization of globin RNA to lambda C beta G1 demonstrates that both globin genes contain major intervening sequences about 800 bp long, similar to those present in mammalian beta-globin genes [13].
• This shift in phenotype correlates with an increase in hemoglobin mRNA specific to both adult and embryonic alpha and beta globin [14].
• A 200 base pair region at the 5' end of the chicken adult beta-globin gene is accessible to nuclease digestion [15].

Anatomical context of VEZF1

• In contrast to Sp1, which is found in a wide variety of cell types, BGP1 is restricted to erythrocytes and is most abundant in definitive erythrocytes [11].
• Using the gel mobility shift assay and a monoclonal antibody that blocks specific binding to the G-string, we have identified a specific protein, BGP1, that is found only in chicken erythroid cells and appears at the same time, or shortly before, the changes in chromatin structure [11].
• As a control, the beta-globin gene, which is not transcribed in oviduct cells, was found not to be preferentially associated with the oviduct nuclear matrix [16].
• This leads us to propose a model for the insulator's ability to protect against extinction in the transformed cell lines and to function as a chromatin boundary for the chicken beta-globin locus in normal erythroid cells [17].
• This effect was most prominently observed in reticulocytes where heat shock almost completely repressed alpha- and beta-globin synthesis [18].

Associations of VEZF1 with chemical compounds

• Correlation between histone lysine methylation and developmental changes at the chicken beta-globin locus [19].
• The promoter region of the chicken adult beta-globin gene contains a sequence of 16 deoxyguanosine residues located at a nucleosome boundary in tissues where the gene is inactive [11].
• We also find that the region between the beta-globin locus and the folate receptor gene is fully methylated and condensed at this stage of differentiation [20].
• The inhibitory action of the RCE was not specific to the beta globin gene since the Herpes thymidine kinase and Xenopus 5S RNA gene transcript levels were similarly reduced [21].
• The globin mRNA is polyadenylylated and is translated into adult chicken alpha A-, alpha D-, and beta-globin polypeptides [22].

Physical interactions of VEZF1

• 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 [23].

Regulatory relationships of VEZF1

• The beta-globin and histone H5 genes were more accessible than the repressed vitellogenin and ovalbumin genes to aflatoxin B1 modification in mature and immature erythroid chromatin [24].

Other interactions of VEZF1

• The 5'-HS4 chicken beta-globin insulator is a CTCF-dependent nuclear matrix-associated element [25].
• The rho globin ought to be functionally equivalent to the adult chicken beta globin [26].
• Incubation of chicken reticulocytes at elevated temperatures (43 to 45 degrees C) resulted in a rapid change in the pattern of protein synthesis, characterized by the decreased synthesis of normal proteins, e.g., alpha and beta globin, and the preferential and increased synthesis of only one heat shock protein, HSP70 [27].
• We find that ovalbumin and alpha 2-collagen gene fragments in erythrocyte chromatin and an adult beta-globin gene fragment in spleen chromatin sediment with bulk chromatin fragments of the same DNA size, whereas the beta-globin gene fragment in erythrocyte chromatin sediments more slowly than bulk fragments of equivalent size [28].
• Chromatin immunoprecipitation of dimethylated lysine 9 on histone H3 across 53 kilobases of the chicken beta-globin locus during erythropoiesis shows an almost complete anticorrelation between regions of elevated lysine 9 methylation and acetylation [19].

Analytical, diagnostic and therapeutic context of VEZF1

• Restriction enzyme analysis of the adult beta-globin gene on lambda C beta G1 is consistent with the hypothesis that its two intervening sequences occur in the same positions with respect to the beta-globin amino acid sequence as do the corresponding mammalian intervening sequences [13].
• The distribution of core histone acetylation across the chicken beta-globin locus has been mapped in 15 day chicken embryo erythrocytes by immunoprecipitation of mononucleosomes with an antibody recognizing acetylated histones, followed by hybridization probing at several points in the locus [29].
• The molecular cloning and nucleotide sequence analysis of adult chicken beta globin mRNA is reported [30].
• Sequence analysis of several clones coding for beta globin strongly suggests that transcription errors may be generated near the 5' end of transcripts in vitro by reverse transcription [30].
• Moreover, the vector containing the 5'HS4 region from the LCR of the chicken beta-globin locus seems appropriate not only for xenotransplantation but also for any other studies involving transgenic animals in which cDNAs have to be expressed at a high level in all cell types [31].

References