Disease relevance of HBZ

• Clones of human embryonic alpha-like zeta-globin cDNA were isolated, by detection using cross-hybridization to human alpha-globin cDNA probes, from a cDNA library derived from the mRNA of the human erythroleukemia cell line K562 [1].
• Alpha-thalassemia was diagnosed by Southern hybridization of subject's DNA to alpha-, and zeta-globin gene fragments, and to Lo probe if needed [2].
• The growth-promoting activity of HBZ RNA likely plays an important role in oncogenesis by HTLV-I [3].
• HBZ, a new important player in the mystery of adult T-cell leukemia [4].
• Less is known about the other regulatory proteins encoded in this region of the provirus, including the recently discovered HBZ protein [5].

High impact information on HBZ

• The ability to detect zeta-globin chains may be useful in populations in which the gene frequency of the greater than 17.5-kb deletion is high, for screening couples at risk of having offspring with homozygous alpha-thalassemia [6].
• Embryonic zeta-globin chains in adults: a marker for alpha-thalassemia-1 haplotype due to a greater than 17.5-kb deletion [6].
• The structure of the human zeta-globin gene and a closely linked, nearly identical pseudogene [7].
• Both zeta-globin genes differ from all other alpha-like genes thus far reported in that they contain large introns consisting, in part, of simple repeat sequences [7].
• The putative polypeptide is 141 amino acids long, identical to that of the alpha- or zeta-globin, but its predicted amino-acid sequence is nearly as different from the orang-utan alpha-globin (55 differences) as the human zeta-globin is from the human alpha-globin (59 differences), suggesting an ancient history for the theta 1-globin gene [8].

Chemical compound and disease context of HBZ

• Here we show that a gene encoded by the minus strand of the HTLV-I proviral genome, HTLV-I basic leucine zipper factor (HBZ), is transcribed from 3'-LTR in all ATL cells [3].

Biological context of HBZ

• Cloning and nucleotide sequence analysis of human embryonic zeta-globin cDNA [1].
• Nucleotide sequence analysis of these cDNA clones revealed a coding sequence that corresponds perfectly to the independently derived amino acid sequence of the human zeta-globin chain [1].
• Nevertheless, the human zeta-globin cDNA sequence shares a remarkable similarity to that of the alpha-globin gene in its codon usage, high G + C base composition, and lack of bias against usage of CG dinucleotides [1].
• When transfected into K562 cells, which express zeta-globin, comparable amounts of activity were obtained from the -557 and -417 zeta-luciferase constructs and the alpha-luciferase constructs when no enhancers or the alpha-globin locus enhancers were used [9].
• BACKGROUND: Information about the appearance of gamma-, epsilon-, and zeta-globin mRNAs in fetal erythroblasts during gestation and about the presence and amounts of these mRNAs in pregnant and nonpregnant women is important from the perspective of using these molecules as a marker of fetal erythroblasts [10].

Anatomical context of HBZ

• Activation of the human beta-globin promoter in K562 cells by DNA sequences 5' to the fetal gamma- or embryonic zeta-globin genes [11].
• As primitive erythroblasts mature from proerythroblasts to reticulocytes, they undergo a betaH1- to epsilony-globin switch, up-regulate adult beta1- and beta2-globins, and down-regulate zeta-globin [12].
• Moreover, embryonic zeta-globin and epsilon-globin chains were present in some of her circulating erythrocytes [13].
• In normal fetuses zeta globin and epsilon globin expression decreased after 12 to 14 weeks, potentially limiting the utility of these proteins as fetal cell markers in the isolation of fetal cells from maternal blood [14].
• Comparison of haemoglobin H inclusion bodies with embryonic zeta globin in screening for alpha thalassaemia [15].

Associations of HBZ with chemical compounds

• We showed that the exchange of human zeta-globin for human alpha-globin chains increased haemoglobin O2 affinity, both in the presence and in the absence of 2, 3-bisphosphoglycerate (2,3-BPG), and reduced the pH-dependent shift in its oxygen equilibrium curve (Bohr effect) [16].
• We show that TF Target Mapper efficiently extracted information on genes around ChIPed sequences, thus identifying known (e.g. alpha-globin and zeta-globin) and potentially novel GATA-1 gene targets [17].
• However, we demonstrate that the HBZ/CREB-2 heterodimers are no more able to bind to the TxRE and cyclic AMP response element sites [18].
• A factor binding GATAAG confers tissue specificity on the promoter of the human zeta-globin gene [19].
• This change may confer a higher intrinsic O2 affinity on the zeta globin protein, ensuring a sufficient O2 supply for the developing goat embryo [20].

Other interactions of HBZ

• Expression of embryonic zeta-globin and epsilon-globin chains in a 10-year-old girl with congenital anemia [13].
• Our results support the hypothesis that HBZ could be a negative modulator of the Tax effect by controlling Tax expression at the transcriptional level and by attenuating activation of AP-1 by Tax [21].
• We then characterized the interaction between HBZ and the cellular transcription factor CREB [5].
• HBZ is a nuclear basic leucine zipper protein that down-regulates Tax-dependent viral transcription by inhibiting the binding of cAMP-response element-binding protein-2 to the HTLV-I promoter [21].
• Cell type-specific protein-DNA interactions in the human zeta-globin upstream promoter region: displacement of Sp1 by the erythroid cell-specific factor NF-E1 [22].

Analytical, diagnostic and therapeutic context of HBZ

• Extensive restriction mapping of 76 human genomic DNAs defines multiple sites of length and point mutation near the zeta-globin locus, which codes for an embryonic alpha-like globin chain [23].
• Recently, 4 studies reported on the existence of different HBZ isoforms and have investigated on their function in both ATL cells or animal models [4].
• Co-immunoprecipitation and cellular colocalization confirmed that HBZ interacts in vivo with JunB and c-Jun [21].
• These results indicate that zeta-globin chains, which can be assayed by immunologic techniques, can serve as markers for the alpha-thalassemia-1 haplotype due to the greater than 17.5-kb deletion [6].
• Gene mapping of the zeta-alpha-globin gene cluster was performed in 12 newborns in whom cord blood zeta-globin chains had been determined [24].

References