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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The location in the mouse genome of the 149-base pair MES-1 element, previously isolated by its ability to restore expression to an enhancerless selectable gene, was analyzed. The active moiety of the single-copy MES-1 element is located between the 5' ends of two divergent transcription units, SURF-1 and SURF-2, both of which specify more than one mRNA species by differential splicing. The heterogeneous 5' ends of the SURF transcripts are separated by only 50 to 75 base pairs, and this sequence possesses a high G + C content (65%) and contains neither the TATA and CAAT box motifs normally associated with many highly expressed genes nor the GC box motif (Sp1-binding site) associated with a number of housekeeping genes. Although MES-1 appears to have enhancerlike properties when linked to heterologous genes, its normal genomic location suggests that it functions as a bidirectional promoter. Thus, MES-1 may represent a new class of enhancer-promoter element.
Mol Cell Biol 1986 Dec
PMID:The MES-1 murine enhancer element is closely associated with the heterogeneous 5' ends of two divergent transcription units. 302 60

The complete 5' flanking region of the murine c-Ha-ras gene was cloned and sequenced. An untranslated exon (-1) was identified and the promoter region of the gene located. Like the rat and human homologues, the murine promoter is GC rich and contains several GC boxes together with a CAAT element, but lacks a TATA box, an arrangement similar to that found in many housekeeping genes. From primer extension studies, the gene was shown to have three transcriptional start sites, whose positions differ from those previously found for the human gene. No alterations in these start sites were detected between the normal gene and activated Ha-ras genes from mouse skin tumors. A region of strong homology between mouse, rat, and human Ha-ras genes exists within the large intron separating exon (-1) from the first coding exon. In addition, from chloramphenicol acetyltransferase assays, the upstream region has promoter activity which appears to be enhanced by the inclusion of sequences within this intron.
Mol Carcinog 1988
PMID:Isolation and characterization of the 5' flanking region of the mouse c-Harvey-ras gene. 307 12

The genes for four glycolytic enzymes of Trypanosoma brucei have been analyzed. The proteins encoded by these genes show 38-57% identity with their counterparts in other organisms, whether pro- or eukaryotic. These data are consistent with a phylogenetic tree in which trypanosomes diverged very early from the main branch of the eukaryotic lineage. No definite conclusion can be drawn yet about the evolutionary origin of glycosomes, the microbodies of trypanosomes which contain most enzymes of the glycolytic pathway. A bias could be observed in the codon usage of the glycolytic genes and genes for other housekeeping proteins, indicating that trypanosomes may have selected a nucleotide sequence that enables efficient translation. However, the genes for variant surface glycoproteins (VSGs) do not show such a bias. This lack of preference for special codons is explained by the high evolutionary rate that could be observed for VSG genes.
J Mol Evol 1986
PMID:Evolutionary aspects of trypanosomes: analysis of genes. 310 18

The compositional distribution of coding sequences from five vertebrates (Xenopus, chicken, mouse, rat, and human) is shifted toward higher GC values compared to that of the DNA molecules (in the 35-85-kb size range) isolated from the corresponding genomes. This shift is due to the lower GC levels of intergenic sequences compared to coding sequences. In the cold-blooded vertebrate, the two distributions are similar in that GC-poor genes and GC-poor DNA molecules are largely predominant. In contrast, in the warm-blooded vertebrates, GC-rich genes are largely predominant over GC-poor genes, whereas GC-poor DNA molecules are largely predominant over GC-rich DNA molecules. As a consequence, the genomes of warm-blooded vertebrates show a compositional gradient of gene concentration. The compositional distributions of coding sequences (as well as of DNA molecules) showed remarkable differences between chicken and mammals, and between mouse (or rat) and human. Differences were also detected in the compositional distribution of housekeeping and tissue-specific genes, the former being more abundant among GC-rich genes.
J Mol Evol 1987
PMID:Compositional compartmentalization and gene composition in the genome of vertebrates. 312 67

The human 4F2 cell surface antigen is a 120-kilodalton (kDa) disulfide-linked heterodimer which is composed of an 80- to 90-kDa glycosylated heavy chain (4F2HC) and a 35- to 40-kDa nonglycosylated light chain (4F2LC). 4F2 belongs to a family of inducible cell surface molecules which are involved in T-lymphocyte activation and growth. To better understand the molecular mechanism(s) that controls 4F2HC gene expression in both resting and activated T cells, a 4F2HC human genomic clone was isolated and structurally characterized. The 4F2HC gene spans 8 kilobases of chromosome 11 and is composed of nine exons. The 5' upstream region of the gene displays several properties which are characteristic of housekeeping genes. It is G+C rich and hypomethylated in peripheral blood lymphocyte DNA and contains multiple binding sites for the Sp1 transcription factor while lacking TATA or CCAAT sequences. This region of the gene also displays sequence homologies with several other inducible T-cell genes, including the interleukin-2, interleukin-2 receptor alpha chain, dihydrofolate reductase, thymidine kinase, and transferrin receptor genes. A 255-base-pair fragment of the 4F2HC gene which contains 154 base pairs of the 5' flanking sequence was able to efficiently promote expression of the bacterial chloramphenicol acetyltransferase gene in human Jurkat T cells, indicating that it contains promoter or enhancer (or both) sequences. Analyses of chromatin structure in resting and lectin-activated T cells revealed the presence of stable DNase I-hypersensitive sites within both the 5' flanking and intron 1 regions of the 4F2HC gene. Although the 4F2HC gene displayed many of the structural features characteristic of a constitutively expressed gene, lectin-mediated activation of resting peripheral blood T lymphocytes resulted in a dramatic increase in steady-state levels of 4F2HC mRNA.
Mol Cell Biol 1988 Sep
PMID:Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation. 326 70

Tropomyosin (TM), a ubiquitous protein, is a component of the contractile apparatus of all cells. In nonmuscle cells, it is found in stress fibers, while in sarcomeric and nonsarcomeric muscle, it is a component of the thin filament. Several different TM isoforms specific for nonmuscle cells and different types of muscle cell have been described. As for other contractile proteins, it was assumed that smooth, striated, and nonmuscle isoforms were each encoded by different sets of genes. Through the use of S1 nuclease mapping, RNA blots, and 5' extension analyses, we showed that the rat alpha-TM gene, whose expression was until now considered to be restricted to muscle cells, generates many different tissue-specific isoforms. The promoter of the gene appears to be very similar to other housekeeping promoters in both its pattern of utilization, being active in most cell types, and its lack of any canonical sequence elements. The rat alpha-TM gene is split into at least 13 exons, 7 of which are alternatively spliced in a tissue-specific manner. This gene arrangement, which also includes two different 3' ends, generates a minimum of six different mRNAs each with the capacity to code for a different protein. These distinct TM isoforms are expressed specifically in nonmuscle and smooth and striated (cardiac and skeletal) muscle cells. The tissue-specific expression and developmental regulation of these isoforms is, therefore, produced by alternative mRNA processing. Moreover, structural and sequence comparisons among TM genes from different phyla suggest that alternative splicing is evolutionarily a very old event that played an important role in gene evolution and might have appeared concomitantly with or even before constitutive splicing.
Mol Cell Biol 1988 Feb
PMID:The rat alpha-tropomyosin gene generates a minimum of six different mRNAs coding for striated, smooth, and nonmuscle isoforms by alternative splicing. 335 2

In a comprehensive study, the temporal replication of tissue-specific genes and flanking sequences was compared in nine cell lines exhibiting different tissue-specific functions. Some of the rules we have determined for the replication of these tissue specific genes include the following. (i) Actively transcribed genes usually replicate during the first quarter of the S phase. (ii) Some immunoglobulin genes replicate during the first half of S phase even when no transcriptional activity is detected but appear to replicate even earlier in cell lines where they are transcribed. (iii) Nontranscribed genes can replicate during any interval of S phase. (iv) Multigene families arranged in clusters of 250 kilobases or less define a temporal compartment comprising approximately one-quarter of S phase. While these rules, and others that are discussed, apply to the tissue-specific genes studied here, all tissue-specific genes may not follow this pattern. In addition, housekeeping genes did not follow some of these rules. These results provide the first molecular evidence that the coordinate timing of replication of contiguous sequences within a multigene family is a general property of the mammalian genome. The relationship between replication very early during S phase and the transcriptional activity within a chromosomal domain is discussed.
Mol Cell Biol 1988 May
PMID:Replication program of active and inactive multigene families in mammalian cells. 338 34

We undertook cloning and sequencing of the 5' portion of the human aldolase A gene to elucidate the mechanisms that govern synthesis of its different mRNAs. The sequenced gene is the only active gene in human-rodent fibroblastic somatic hybrids, while the other aldolase A-related sequences are inactive. S1 mapping and primer extension analysis enabled us to demonstrate that three promoter regions were implicated in the initiation of different aldolase A mRNAs, differing only in their 5' non-coding extremities. A distal promoter, N (non-specific), governs the synthesis of a 5' non-coding region of 142 bases composed of two exons, N1 and N2, which are found in a variety of tissues. A median promoter, M (muscle), is only active in skeletal muscle, and initiates the transcription by a 5' non-coding exon of 45 bases. Finally, a proximal promoter, H (housekeeping), contained in a "G + C-rich island", permits transcription of three colinear mRNAs containing 172, 126 or 112 bases of 5' non-coding sequence; their expression seems ubiquitous. These three promoters are arranged in 1.5 X 10(3) base-pairs of DNA. Homologies between rat and human genomic sequences and the absence of homology between promoters or 5' non-coding exons of the same species exclude a recent duplication of the promoter regions.
J Mol Biol 1987 Oct 05
PMID:Characterization of three optional promoters in the 5' region of the human aldolase A gene. 344 Oct 6

DNA sequences complementary to six mammalian ribosomal protein (r-protein) cDNAs are assigned to human chromosomal linkage groups in human-Chinese hamster hybrid cell clones. Ten r-protein DNA fragments map to chromosomes 5, 8 and 17, indicating that these important, housekeeping genes are distributed to multiple sites in the human genome. Each of the chromosome assignments, determined initially by surveying Chinese hamster-human hybrid cell clones with complex karyotypes using Chinese hamster and human cDNA probes, were confirmed in critical minipanels of highly reduced or monochromosomal hybrid cells. As all 10 fragments mapped to only three human chromosomes, r-protein sequences appear to be distributed nonrandomly within human DNA. The r-protein S14 sequence assigned to human chromosome 5 (5q23-5q33) rescues Chinese hamster emetine-resistance mutations (emt b) in interspecific hybrids. Therefore, this sequence corresponds to the transcriptionally active human RPS14 gene. In contrast, other r-protein DNA sequences examined likely are a mixture of functional genes and inactive pseudogenes.
Somat Cell Mol Genet 1986 May
PMID:Ribosomal protein gene sequences map to human chromosomes 5, 8, and 17. 345 54

We cotransformed mouse 3T3 cells with total genomic human DNA and the dominant selectable bacterial gene Neo and analyzed 121 NeoR clones for expression of 15 human "housekeeping" enzymes which can be distinguished from their murine homologs. The estimated frequency of expression of unlinked human genes was 1 in 360 NeoR clones and at least three different human enzymes (peptidase D, phosphoglucomutase 1, and acid alpha glucosidase) were detected. We further examined the frequency and stability of cotransformation for one of these enzymes, acid alpha glucosidase (GAA). We tested approximately 4000 NeoR clones and found 25 clones expressing human GAA, as determined by rocket immunoelectrophoresis (RIE) specific for human GAA. Transformants progressively became negative on continued growth and retesting by RIE, with only two clones still expressing GAA at the eighth testing. This apparent loss of expression was not due to nonclonality of the original isolates. In one subclone examined, loss of expression was accompanied by loss of both Neo-derived pBR322 and human Alu repetitive sequence DNA. Thus, under the conditions utilized, cotransformants expressing homomeric housekeeping enzymes were found at relatively high frequency but were progressively lost even under conditions selective for expression of the dominant vector.
Somat Cell Mol Genet 1986 Jan
PMID:Detection, frequency, and stability of cotransformants expressing nonselectable human enzymes. 351 43


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