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Query: UNIPROT:P06889 (Mol)
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The elements regulating lens-specific expression of the mouse gamma F-crystallin gene were examined. Here we show that mouse gamma F-crystallin sequences -67 to +45 contain a low basal level of lens-specific promoter activity and that sequences -67 to -25, which are highly conserved among different gamma-crystallin genes, are able to function as a strong transcriptional activator when duplicated and placed upstream of the TATA box. We also show that nuclear factors from lens and nonlens cells are able to form different complexes with sequences centered at -46 to -36 and demonstrate that binding of the factor from lens cells correlates with lens-specific promoter activity of the mouse gamma F-crystallin gene.
Mol Cell Biol 1991 Mar
PMID:Interaction of a lens cell transcription factor with the proximal domain of the mouse gamma F-crystallin promoter. 199 7

A search of sequence databases shows that spherulin 3a, an encystment-specific protein of Physarum polycephalum, is probably structurally related to the beta- and gamma-crystallins, vertebrate ocular lens proteins, and to Protein S, a sporulation-specific protein of Myxococcus xanthus. The beta- and gamma-crystallins have two similar domains thought to have arisen by two successive gene duplication and fusion events. Molecular modeling confirms that spherulin 3a has all the characteristics required to adopt the tertiary structure of a single gamma-crystallin domain. The structure of spherulin 3a thus illustrates an earlier stage in the evolution of this protein superfamily. The relationship of beta- and gamma-crystallins to spherulin 3a and Protein S suggests that the lens proteins were derived from an ancestor with a role in stress-response, perhaps a response to osmotic stress.
J Mol Evol 1990 Feb
PMID:Evolution of a protein superfamily: relationships between vertebrate lens crystallins and microorganism dormancy proteins. 210 29

The structures of the two very closely related proteins, bovine gamma II- and gamma IVa-crystallin have been studied by means of near-ultra-violet linear dichroism spectroscopy on squeezed polyacrylamide gel systems. The crystallin spectra are discussed in terms of the spectra of the aromatic chromophores present in these proteins and provide detailed information on the average orientation of these residues in the proteins. A comparison of our results with information based on crystallographic X-ray experiments shows excellent agreement, reflecting even some of the minor differences between the two proteins studied. Since linear dichroism measurements as performed here take a few days only, and can be done on most aqueous protein solutions, linear dichroism spectroscopy may give a valuable contribution to structural studies on proteins.
J Mol Biol 1990 Nov 05
PMID:Average orientation of aromatic residues in proteins determined from linear dichroism spectroscopy. A comparison of results on bovine gamma-crystallins with X-ray data. 223 30

One copy of the mouse alpha A-crystallin gene alpha A-CRYBP1 site activated the thymidine kinase (tk) promoter in a mouse lens epithelial cell line but not in primary chicken lens cells; multiple copies further activated the tk promoter and extended expression to fibroblasts, B cells, and chicken lens cultures. The loss of lens specificity by multimerization may place selective constraints on the number of alpha A-CRYBP1 sites in the alpha A-crystallin promoter.
Mol Cell Biol 1990 Dec
PMID:Species-specific lens activation of the thymidine kinase promoter by a single copy of the mouse alpha A-CRYBP1 site and loss of tissue specificity by multimerization. 224 86

During hominoid evolution the gamma-crystallins of the lens have decreased in quantity as well as complexity, a change correlated with an increased water content of the lens. To trace the molecular basis for the decrease in gamma-crystallin gene expression, we have characterized the structure and expression of the human gamma-crystallin gene family. We show that the human gamma-crystallin gene family consists of six complete genes (gamma A, gamma B, gamma C, gamma D, psi gamma E and psi gamma F) and one second exon fragment, the gamma G gene. Model experiments showed that, although the gamma G sequence is bordered by consensus splice sites, it is most likely transcriptionally inactive in the lens. In the human embryonic lens the gamma C and gamma D genes accounted for 81% of the gamma-crystallin transcripts, the gamma A gene contributed 14% and the gamma B gene only 5%. The composition of the gamma-crystallin mRNA pool changed only after birth, with the gamma D transcript as the only detectable transcript at ten years of age. The relative activities of the gamma A, gamma C and gamma D promoters in a transient expression system were in agreement with the ratio of their in vivo RNA levels, suggesting that the difference in accumulation of these transcripts is due to differences in the rate of transcription. The gamma B promoter was much more active than expected and had lost its tissue-specificity. Model experiments showed that the low yield of the gamma B transcript is due to post-transcriptional processes, most likely RNa instability mediated by third exon sequences. Together with previous data, our results show that the decrease in expression of the gamma-crystallin genes in the human lens is the consequence of gene loss (gamma G), inactivation of coding sequences (psi gamma E and psi gamma F), decrease in rate of transcription (gamma A), increase in rate of RNA turn-over (gamma B) and a delay in the onset of transcription during development.
J Mol Biol 1990 Dec 05
PMID:Human gamma-crystallin genes. A gene family on its way to extinction. 225 29

A major component of the soluble fraction of rat heart is a homopolymer (Mr about 400-650 k) of a small protein (Mr about 20 k). This cardiac protein, which is highly homologous to alpha-B-crystallin, was isolated in its native state and visualized by electron microscopy. A homogeneous population of globular particles with an average diameter of about 14-16 nM could be seen using either negative staining or rotary shadowing procedures. The structures were globular in nature with a central depression (torus-like structures). Polyclonal antibodies, raised against the cardiac crystallin, were used for the immunocytochemical localization of the macromolecular complexes. Using fluorescent secondary antibodies, a clear and sharp striation of fixed and permeabilized rat heart myocytes could be observed, similar to that observed with anti-desmin antibodies and characteristic for the central region of the I-band. Cardiac crystallin was not found associated with F-actin in preparations of rat heart myofibrils. On the other hand, it was a major contaminant of cardiac desmin preparations. These observations suggest that cardiac crystallin is involved in the organization of cytoskeletal filaments of the Z-lines.
Mol Cell Biochem 1990 Sep 21
PMID:Cardiac alpha-crystallin. II. Intracellular localization. 228 Jul 60

Rat hearts were perfused in the working heart or Langendorff mode and then subjected to total normothermic ischemia. The content of alpha-crystallin in the water soluble protein fraction obtained from these hearts diminished in a time-dependent manner during ischemia. The protein was recovered in the low g pellet of the homogenate. The redistribution was dramatic, selective for alpha-crystallin and irreversible. Large crystallin clumps formed also when exposing the soluble protein fraction of control hearts to slightly acidic pH (6.5-7.0). Electron microscopic analysis showed that aggregation of the globular homo-oligomeric units of crystallin occurred. The aggregates probably represented denatured protein and were similar in appearance to lenticular alpha H-crystallin. In purified form, however, cardiac crystallin particles did not cluster at pH 6.5. Aggregation only occurred in the presence of other protein components (including, probably, cytosolic actin) of the soluble fraction. A direct and selective interaction between actin and cardiac crystallin could be demonstrated using actin-Sepharose affinity chromatography procedures. The results suggest that large aggregates of cardiac crystallin form very early during ischemia, due to acidification of the cytosol. Cardiac crystallin is highly homologous to stress proteins and is localized on the Z-disks, where it plays probably a structural or protective role. Its rapid and complete denaturation could be involved in the genesis of the irreversible structural damages occurring during ischemia.
Mol Cell Biochem 1990 Sep 21
PMID:Cardiac alpha-crystallin. III. Involvement during heart ischemia. 228 Jul 61

The 18S ribosomal RNAs of 21 tetrapods were sequenced and aligned with five published tetrapod sequences. When the coelacanth was used as an outgroup, Lissamphibia (living amphibians) and Amniota (amniotes) were found to be statistically significant monophyletic groups. Although little resolution was obtained among the lissamphibian taxa, the amniote sequences support a sister-group relationship between birds and mammals. Portions of the 28S ribosomal RNA (rRNA) molecule in 11 tetrapods also were sequenced, although the phylogenetic results were inconclusive. In contrast to previous studies, deletion or down-weighting of base-paired sites were found to have little effect on phylogenetic relationships. Molecular evidence for amniote relationships is reviewed, showing that three genes (beta-hemoglobin, myoglobin, and 18S rRNA) unambiguously support a bird-mammal relationship, compared with one gene (histone H2B) that favors a bird-crocodilian clade. Separate analyses of four other genes (alpha-crystallin A, alpha-hemoglobin, insulin, and 28S rRNA) and a combined analysis of all sequence data are inconclusive, in that different groups are defined in different analyses and none are strongly supported. It is suggested that until sequences become available from a broader array of taxa, the molecular evidence is best evaluated at the level of individual genes, with emphasis placed on those studies with the greatest number of taxa and sites. When this is done, a bird-mammal relationship is most strongly supported. When regarded in combination with the morphological evidence for this association, it must be considered at least as plausible as a bird-crocodilian relationship.
Mol Biol Evol 1990 Nov
PMID:Tetrapod phylogeny inferred from 18S and 28S ribosomal RNA sequences and a review of the evidence for amniote relationships. 156 Jul 70

We have previously generated microphthalmic mice lacking lens fiber cells by targeting the expression of the diphtheria toxin A (DT-A) gene in transgenic mice with regulatory sequences associated with the mouse gamma 2-crystallin gene. Because of the extreme toxicity of DT to animal cells and the potential leakiness of many tissue-specific regulatory regions, we investigated whether there might be an experimental advantage in using a mutant, attenuated form of the DT-A gene (tox-176) fused to gamma 2-crystallin regulatory sequences to ablate fiber cells in the ocular lens. In contrast to the microphthalmia observed in transgenic animals carrying the native DT-A gene, independent lines of mice transgenic for the gamma 2tox176 construct displayed predominantly cataracts or clinical anophthalmia. These contrasting phenotypes were transmitted within each pedigree, although for some lines some phenotypic heterogeneity among offspring was noted. The difference in phenotype between cataractous and clinically anophthalmic transgenic lines could not be ascribed to differences in the transgene copy number. Instead, the results suggest that transgene expression and hence the extent of genetic ablation are modulated by the site of chromosomal integration and, to a lesser extent, by epigenetic events. They also suggest that the attenuated gamma 2tox176 construct can integrate into chromosomal regions that are particularly favorable for expression without compromising embryological development and therefore that the tox-176 gene may be more versatile and effective than the wild-type DT-A gene for achieving genetic ablation with a broad range of cell- or tissue-specific regulatory sequences.
Mol Cell Biol 1990 Feb
PMID:Genetic ablation in transgenic mice with an attenuated diphtheria toxin A gene. 230 48

The expression of the chicken delta 1-crystallin gene is primarily regulated by the action of a lens-specific enhancer 1 kilobase long and located in the third intron of the gene (S. Hayashi, K. Goto, T. S. Okada, and H. Kondoh, Genes Dev. 1:818-828, 1987). The 120-base-long core segment is required for the activity of the delta 1-crystallin enhancer but by itself shows no activity. We analyzed the action of the core and adjoining segments of the delta 1-crystallin enhancer by two different approaches: (i) multiplication of the segments to express any cryptic effect and (ii) competition among enhancers for nuclear factors involved in enhancer action. We found that (i) the core defines a strictly lens-specific element, (ii) an adjoining segment defines an element with a broad specificity with regard to cell type, (iii) these elements cooperate in cis within the delta 1-crystallin enhancer, (iv) the multimers of these elements complete with each other and with delta 1-crystallin and simian virus 40 enhancers in trans apparently without sequence specificity but in a fashion reflecting the strength of the enhancers, and (v) the enhancers in trans do not affect the expression of enhancer-free genes, thereby ruling out the possibility of competition for general transcription factors. The last two observations raise the possibility that the enhancer segments interacting with different sequence-specific factors also interact with one other component involved in enhancer action.
Mol Cell Biol 1990 Mar
PMID:Functional cooperation of lens-specific and nonspecific elements in the delta 1-crystallin enhancer. 230 70


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