Disease relevance of glob1

• Of the four known globin genes that exist in the fresh-water crustacean Daphnia magna, several are individually induced by hypoxia, lending pale normoxic animals a visible red color when challenged by oxygen deprivation [1].

High impact information on glob1

• We show here that, although in these two cell types the correspondence between DNase I sensitivity and gene transcription holds good for globin and the ribosomal genes, the tRNA and oogenetic 5S genes are DNase I sensitive in both liver and erythrocyte nuclei [2].
• We show here that both wild-type Pannier and the dominant mutant form activate transcription from the heterologous alpha globin promoter when transfected into chicken embryonic fibroblasts [3].
• For each promoter studied (erythroid pyruvate kinase, glycophorin B, and a murine betamaj globin-derived construct, GCT) Sp1 and EKLF each activated transcription despite differences in CACC element sequence, orientation, and positioning [4].
• In particular, the interaction of GATA-1 with itself and with other transcription factors may facilitate its function at diverse promoters in erythroid cells and also serve to bring together, or stabilize, loops between distant regulatory elements, such as the globin locus control regions and downstream globin promoters [5].
• An unresolved aspect of current understanding of erythroid cell-specific gene expression relates to how a limited number of transcriptional factors cooperate to direct high-level expression mediated by cis-regulatory elements separated over large distances within globin loci [6].

Biological context of glob1

• Gene structure (introns in helix positions D7.0 and G7.0), gene synteny and sequence of glob1 are highly conserved, with high ds/dn ratios indicating strong purifying selection [7].
• These experiments provide the first evidence for functionally important protein-protein interactions involved in erythroid cell-specific expression and suggest a mechanism by which DNA loops between locus control regions and globin promoters (or enhancers) might be formed or stabilized [6].
• To analyze the function of these sites, Drosophila SL-2 cells, which lack Sp1, were cotransfected with an Sp1 expression plasmid and gamma globin promoter-CAT constructs [8].
• The promoter regions of the Daphnia globin genes each contain numerous hypoxia response elements (HREs) as potential binding sites for hypoxia-inducible factors (HIFs) [1].
• It was pointed out that these estimates are consistent with the corresponding estimate Pneut(Hb) = 0.14 obtained independently based on the neutral theory and using data on the evolutionary rate of nucleotide substitutions in globin pseudogenes together with those in the normal globins [9].

Anatomical context of glob1

• Consequently, a role for CP2 has been proposed in globin gene expression, T-cell responses to mitogenic stimulation, and several other cellular processes [10].
• Specifically, no perturbation of hematopoietic differentiation, globin gene expression, or immunological responses to T- and B-cell mitogenic stimulation was observed [10].
• Another important aspect of stem cell gene therapy, the actual expression of the transduced genes, has only been investigated adequately in very few studies, mainly for globin genes [11].
• Experiments with purified globin mRNA injected into frog oocytes and eggs show that macromolecules can retain their activity when injected into living cells [12].

Associations of glob1 with chemical compounds

• Previous results have shown that D. melanogaster hemoglobin 1 (product of the glob1 gene) displays heme endogenous hexacoordination in both the ferrous and ferric states [13].

Regulatory relationships of glob1

• A fusion protein comprised of Neptune's DBD and the Drosophila engrailed repressor domain suppresses the induction of globin in ventral marginal zones and in animal caps [14].

Other interactions of glob1

• We discuss the significance of these findings with regard to Abd-B transvection and long-range enhancer-promoter interactions in mammalian globin loci [15].

References