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Query: UNIPROT:P06889 (Mol)
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Previous transfection experiments have shown that 162 base pairs (bp) of the 5' flanking sequence of the chicken alpha A-crystallin gene are required for promoter activity in primary chicken lens epithelial cells (PLE), while only 111 bp of the 5' flanking sequence are needed for activity of the mouse alpha A-crystallin promoter in transfected chicken PLE cells or in a SV40 T-antigen-transformed transfected mouse lens epithelial cell line (alpha TN4-1). The effect of site-directed mutations covering positions -111 to -34 of the mouse alpha A-crystallin promoter fused to the bacterial chloramphenicol acetyltransferase (CAT) gene was compared in transfected chicken PLE cells and mouse alpha TN4-1 cells; selected mutations were also examined in a nontransformed rabbit lens epithelial cell line (N/N1003A). In general, the same mutations reduced promoter activity in the transfected lens cells from all three species, although differences were noted. The mutations severely affected regions -111/-106 and -69/-40 regions in all the transfected cells examined; by contrast, mutations at positions -105/-99 and -87/-70 had a somewhat greater effect in the chicken PLE than the mouse alpha TN4-1 cells, while mutations of the -93/-88 sequence reduced expression in the alpha TN4-1 but not the PLE cells. A partial cDNA with sequence similarity to alpha A-CRYPB1 of the mouse has been isolated from a chicken lens library; mouse alpha A-CRYBP1 is a putative transcription factor which binds to the -66/-55 sequence of the mouse alpha A-crystallin promoter.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Evol 1992 Oct
PMID:Conservation of mouse alpha A-crystallin promoter activity in chicken lens epithelial cells. 140 19

We have shown by site-directed mutagenesis that the sequence between positions -69 and -40 of the mouse alpha A-crystallin gene is crucial for tissue-specific gene expression in a transfected mouse lens epithelial cell line transformed with the early region of simian virus 40. Gel retardation experiments with synthetic oligodeoxynucleotides revealed a mouse lens nuclear protein which bound specifically to the palindromic sequence 5'-GGGAAATCCC-3' at positions -66 to -57 in the alpha A-crystallin promoter. By screening a bacteriophage lambda gt11 expression library of the transformed lens cells, we isolated a 2.5-kilobase-pair cDNA encoding a fusion protein which bound to this sequence and to the regulatory element of the major histocompatibility complex (MHC) class I gene. This cDNA hybridized to a 10-kilobase-pair polyadenylated RNA present in many different tissues, including lens. It encoded a protein, tentatively called alpha A-CRYBP1, containing at least two zinc fingers. alpha A-CRYBP1 is either homologous or very similar to the human nuclear proteins MBP-1 (Baldwin et al., Mol. Cell. Biol. 10:1406-1414, 1990), PRDII-BFI (Fan and Maniatis, Genes Dev. 4:29-42, 1990), and HIV-EP1 (Maekawa et al., J. Biol. Chem. 264:14591-14593, 1989), which bind to regulatory elements of the MHC class I, beta interferon, and human immunodeficiency virus genes, respectively. Our results suggest that the lens-specific alpha A-crystallin, MHC class I, beta interferon and other genes have a similar cis-acting DNA regulatory motif that shares alpha A-CRYBPI, MBP-1, PRDII-BF1, HIV-EP1, or other closely related proteins as trans-acting factors.
Mol Cell Biol 1990 Jul
PMID:Regulation of the mouse alpha A-crystallin gene: isolation of a cDNA encoding a protein that binds to a cis sequence motif shared with the major histocompatibility complex class I gene and other genes. 169 16

Approximately 2 kb of 5'-flanking sequences of the lens-specific alpha A-crystallin genes from human and mouse are presented and compared with similar regions of the chicken gene. A repetitive element was found approximately 1 kb upstream from the coding sequences of the alpha A-crystallin gene in all three species (Alu in human, B2 in mouse, and CR1 in chicken), suggesting that they may have an important functional or structural role. Despite the ability of alpha A-crystallin promoters to function across species, dot matrix analyses show only limited similarity among the 600 bp 5' to the structural genes of these three species. The human 5'-flanking sequence is more similar to that of the mouse and chicken than the mouse and chicken are to each other. Numerous short sequences (8-13 bp) are common to all three genes but are distributed differently in each species. The locations and conservation of these sequence motifs suggest functional roles, possibly as cis-regulatory elements of transcription. One motif is similar to the alpha A-CRYBP1 binding site implicated earlier in the transcriptional regulation of the mouse alpha A-crystallin gene, and other motifs correspond to sites previously mapped by methylation interference studies in the mouse alpha A-crystallin promoter. The modular arrangement of conserved sequence motifs is consistent with evolutionary changes occurring at the level of gene regulation.
J Mol Evol 1991 Dec
PMID:The alpha A-crystallin gene: conserved features of the 5'-flanking regions in human, mouse, and chicken. 177 32

Transcriptional activation of the rat angiotensinogen gene during the acute-phase response is dependent on a previously characterized acute-phase response element (APRE) that binds at least two types of nuclear proteins: a cytokine-inducible activity indistinguishable from nuclear factor kappa-B (NF kappa B) and a family of C/EBP-like proteins. We screened a rat liver cDNA expression library with a labeled APRE DNA probe and isolated a single clone that encodes a sequence-specific APRE-binding protein. This new protein, the angiotensinogen gene-inducible enhancer-binding protein 1 (AGIE-BP1), is encoded by a large continuous open reading frame and contains a zinc finger motif virtually identical to the DNA-binding domain of a recently described human protein, MBP-1/PRDII-BF1, and a homologous mouse protein, alpha A-CRYBP1. Outside the binding domain, the sequences diverged considerably. Southern blot analysis indicated that AGIE-BP1 and alpha A-CRYBP1 are encoded by separate genes, thus defining a new family of DNA-binding proteins. Electrophoretic mobility shift assays, methylation interference, and DNase I footprint protection assays with the bacterially expressed DNA-binding domain of AGIE-BP1 demonstrated a binding specificity indistinguishable from that of purified NF kappa B. Antiserum raised against the bacterially expressed DNA-binding domain of AGIE-BP1 detected on immunoblots of cellular proteins a large (greater than 250-kDa) nuclear protein. Northern (RNA) blot analysis of RNAs from different rat tissues and cell lines indicated different levels of expression of the large (greater than 10-kb) AGIE-BP1 transcript in different tissues. The potential role of AGIE-BP1 in the regulation of gene expression is discussed.
Mol Cell Biol 1991 May
PMID:Angiotensinogen gene-inducible enhancer-binding protein 1, a member of a new family of large nuclear proteins that recognize nuclear factor kappa B-binding sites through a zinc finger motif. 201 83

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

Genomic footprinting, in vitro footprinting and mobility shift assays were used to investigate the molecular basis for expression of mouse alpha A-crystallin, a major structural protein of the transparent lens of vertebrates. The putative control region of the mouse alpha A-crystallin gene was footprinted by DNase I digestion in nuclear extracts, by dimethylsulfate treatment in cultured cells, and by micrococcal nuclease digestion in isolated nuclei. The resulting digestion patterns were compared between alpha TN4-1 lens cells, which express alpha A-crystallin, and L929 fibroblasts, which do not express alpha A-crystallin. Four regions of DNA were found occupied in both cell types. These included positions -111 to -97 (DE-1 region), positions -75 to -55 (alpha A-CRYBP1 region), positions -35 to -12 (TATA box and PE-1 region), and positions +23 to +43 (an AP-1 consensus sequence). The DNase I footprints of the DE-1 and alpha A-CRYBP1 regions, previously implicated as functional control elements, were substantially more pronounced using nuclear extract from the alpha TN4-1 cells than from the L929 fibroblasts, suggesting more stable protein binding with the former than with the latter. Numerous in vivo binding variations were noted between the two cell types in all four of the footprinted regions examined. Finally, two complexes (A and B) were formed specifically with nuclear extracts from the alpha TN4-1 cells and a synthetic deoxyoligonucleotide comprising the alpha A-CRYBP1 region. These data indicate that specific differences in protein-DNA interactions with putative control regions are associated with tissue-preferred expression of the mouse alpha A-crystallin gene.
J Mol Biol 1993 Mar 20
PMID:Protein-DNA interactions of the mouse alpha A-crystallin control regions. Differences between expressing and non-expressing cells. 846 58