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At least 1,261 records · Page 70Linked to original sources
PubMed1999

Structure of the human gene for lysosomal di-N-acetylchitobiase.

Chitobiase is a lysosomal glycosidase that acts during the ordered degradation of asparagine-linked glycoproteins to cleave the core chitobiose unit at its reducing end. Human chitobiase is expressed in significant amounts, while bovine chitobiase is produced at extremely low levels. To begin to understand this species-dependent expression, we determined the gene structure of human chitobiase. The human chitobiase gene ( CTB S) is approximately 20 kb comprising seven exons varying from 0.1 to 2.3 kb and six introns of 0.3 to 8 kb. The previously characterized partial bovine chitobiase gene structure is similarly organized including exon and intron sizes and locations, but the human and bovine 5'-flanking regions differ significantly. 5'-RACE analysis of human chitobiase cDNA revealed only one transcriptional start site 45 bp upstream of the ATG translation initiation site. Computer analysis of the human chitobiase gene 5'-flanking region shows characteristics of a typical housekeeping gene. The putative promoter region contains a distal TATA box, and there are several Sp-1 and AP-2 cis elements. In contrast, bovine chitobiase gene 5'-flanking region shows totally different structures and may contain several silencers. A partial art-2 segment which is an artiodactyl Alu -like repetitive sequence, is also present. These evolutionary differences in the 5'-flanking region of the chitobiase genes from human and bovine could account for the widely varied expression levels of the hydrolase within these two species.

Amino Acid Sequence↗
PubMed1991

The interleukin-6 gene locus seems to be a preferred target site for retrotransposon integration.

Recently, we have observed the insertion of a retrotransposon into the interleukin-6 (Il-6) locus of a mouse somatic cell line. Here we report the characterization of Il-6 genomic regions from both mouse and rat. Restriction site analysis, DNA sequence analysis, and computer-assisted search revealed eight retrotransposon-like elements distributed over a 25 kilobase (kb) mouse Il-6 region. In the rat, five different retrotransposons have been identified within a 17 kb Il-6 region. The retrotransposons belong to the LINE-, Alu I or Alu II families, or to a rat specific class of retrotransposons. Some of the retrotransposons exhibit characteristic features such as target site duplication and a poly A-tract. Remarkably, several retrotransposons map to different chromosomal locations in the mouse and rat. A genealogical tree of mouse, rat, and human Il-6 loci demonstrates a series of retrotranspositions that recently occurred in evolution. These results suggest that the Il-6 locus serves as a preferred target site for retrotransposon integration during evolution.

Animals↗
PubMed1992

Genomic sequence and chromosomal location of human interleukin-11 gene (IL11).

The genomic sequence of human interleukin-11 (IL11) has been isolated based on its sequence homology with a cDNA clone encoding primate IL11. The human IL11 genomic sequence is 7 kb in length and consists of five exons and four introns. The IL11 gene has been localized to the long arm of human chromosome 19 at band 19q13.3-q13.4 by in situ hybridization. Several potential transcriptional control sequences that may play an important role in the control of IL11 gene expression have been identified within the 5'-flanking region of the human IL11 gene. The 5'-flanking region of the human IL11 gene contains sequences similar to those present in the 5'-regulatory regions of other cytokine genes. Four repeats of a 30-bp DNA segment were found in the fourth intron, and several copies of ATTTA and Alu repetitive sequences were identified in the 3'-noncoding region of the human IL11 gene. A DNA sequence (ACATGGCAAAACCC) that has 71% similarity with the IL1-responsive element of the IL6 gene was found in the 3'-flanking region of the human IL11 gene. The two polyadenylation sites located at nucleotide positions 6762 and 5591 correspond to the 2.5- and 1.5-kb IL11 transcripts expressed in IL1-induced PU-34 cells. The availability of the human IL11 genomic sequence should aid in studies of the regulatory mechanisms of IL11 gene expression in different cell types and the role of IL11 expression in the hematopoietic microenvironment.

Amino Acid Sequence↗
PubMed1998

Promoter analysis of the human mismatch repair gene hMSH2.

The human DNA mismatch repair gene homologue hMSH2 is involved in hereditary nonpolyposis colorectal cancer. We isolated and characterized the 5' upstream region, about 4.4kbp, of the hMSH2 gene. This region contains CpG islands and a number of elements involved in constitutive expression, but there is no TATA-box nearby the transcription start points. This is the typical structure for many promoters of housekeeping genes. Alu sequences and mononucleotide repeats are clustered in this region and there are two transcription start points. Deletion analysis revealed that less than 300bp was sufficient to initiate transcription. Although no mutation that influences promoter activity of this region was found, a polymorphism was detected by PCR-RFLP analysis. Because informative cases (C/T heterozygous) were relatively high ( approximately 30%), this polymorphism is suitable for a marker to examine allelic losses.

Alleles↗
PubMed1997

Characteristic sequence motifs at the breakpoints of the hybrid genes FUS/CHOP, EWS/CHOP and FUS/ERG in myxoid liposarcoma and acute myeloid leukemia.

We have sequenced the breakpoint regions in one acute myeloid leukemia (AML) with t(16;21)(p11;q22) resulting in the formation of a FUS/ERG hybrid gene and in four myxoid liposarcomas (MLS), three of which had the translocation t(12;16) (q13;p11) and a FUS/CHOP fusion gene and one with t(12;22;20)(q13;q12;q11) and an EWS/CHOP hybrid gene. The breakpoints were localized to intron 7 of FUS, intron 1 of CHOP, an intronic sequence of ERG and intron 7 of EWS. In two MLS cases with t(12;16) and in the AML, the breaks in intron 7 of FUS had occurred close to each other, a few nucleotides downstream from a TG dinucleotide repeat region. The break in the two MLS had occurred in the same ATGGTG hexamer and in the AML 40 nucleotides upstream from the hexamer. The third case of t(12;16) MLS had a break upstream and near a TC-dinucleotide repeat region and a sequence similar to the chi bacterial recombination element was found to flank the breakpoint. In the MLS with the EWS/ CHOP hybrid gene, the break in intron 7 of EWS had occurred close to an Alu sequence. Similarly, in all 4 MLS, the breaks in intron 1 of CHOP were near an Alu sequence. No Alu or other repetitive sequences were found 250 bp upstream or downstream from the break in the ERG intron involved in the AML case. In the AML, the MLS with ESW/CHOP and in one MLS with FUS/CHOP there were one, two and six, respectively, nucleotide identity between the contributing germline sequences in the breakpoint. In the other two MLS cases, two and three extra nucleotides of unknown origin were inserted between the FUS and CHOP sequences. At the junction and/or in its close vicinity, identical oligomers, frequently containing a trinucleotide TGG, were found in both partner genes. Our data thus show that all four genes-FUS, EWS, CHOP and ERG-contain characteristic motifs in the breakpoint regions which may serve as specific recognition sites for DNA-binding proteins and have functional importance in the recombination events taking place between the chromosomes. Different sequence motifs may, however, play a role in each individual case.

Acute Disease↗
PubMed1984

Transcription of two classes of rat growth hormone gene-associated repetitive DNA: differences in activity and effects of tandem repeat structure.

The rat growth hormone (rGH) gene contains two classes of repetitive DNA arranged as clusters within intron B and the 3' flanking region. The major family is equivalent to the CHO type 2 DNA. The second ("truncated repeat", TR) is a truncated version of the first and occurs in certain neural-specific transcripts and genes ("identifier" elements, ID). Here we report, using the HeLa cell-free transcription assay, that RNA polymerase III (Pol III) efficiently initiates at internal promoters within a tandem array of rGH gene repetitive DNA monomers and results in a novel organization of overlapping Class III transcription units. Transcription competition studies revealed that the rat type 2 structures share Pol III transcription factors with a tRNA gene, a human Alu repeat, and a mutant VA1 gene. Also, the rGH type 2 but not the TR DNA efficiently promotes Pol III initiation, yet other TR members, which differ only in flanking DNA, are transcribed. Thus, the rGH gene is strikingly enriched with 10 repetitive DNA monomers; multimeric type 2 elements are actively transcribed; rGH-TR sequences are expressed only as part of larger transcripts promoted by type 2 DNA; and, type 2 DNA uses tRNA gene transcription factors. These studies show that flanking sequences, promoter organization and factor competition may all affect rat repetitive DNA expression.

Animals↗
PubMedDate not supplied

Identification of new medium reiteration frequency repeats in the genomes of Primates, Rodentia and Lagomorpha.

We report eleven new families of MEdium Reiteration frequency (MER) interspersed repeats in the genomes of Primates, Rodentia, and Lagomorpha. Two families of the human repeats, MER 46 and MER 47, represent non-autonomous DNA transposons. These sequences are flanked by TA target site duplications and have terminal inverted repeats (TIRs) similar to TIRs of DNA transposons. The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses. A potential involvement of some of the reported MER repeats in the regulation of transcription and genetic rearrangements is suggested. Age estimations place the origin of most MER repeats at the time of decline in MIR (Mammalian-wide Interspersed Repeats) retroposition and before the origin of the Alu family.

Animals↗
PubMed2005

Short retroposons in eukaryotic genomes.

Short retroposons (SINEs) are repetitive elements amplified in the genome via an RNA intermediate, using the enzymatic machinery of autonomous retroposons (LINEs). SINEs are widely distributed in eukaryotes; for instance, all tested mammalian genomes contain 10(4)-10(6) SINE copies. Although several SINE families such as primate Alu or rodent B1 have long been recognized, the more recent discovery of many SINEs in various eukaryotes, as well as progress in understanding the mechanisms of LINE replication and genome functioning as a whole, shed light on the biology and evolution of SINEs and their significance for the cell.

Animals↗
PubMed1985

Structure of the chromosomal gene for human serum prealbumin.

The human prealbumin gene has been cloned and its complete nucleotide sequence determined. The gene has a size of about 6.9 kb and is composed of four exons and three introns. Two Alu family sequences having opposing polarity were found in introns. In the 5'-flanking region, we found two overlapping sequences which have extensive homology to the glucocorticoid-responsive element. Three sequences identical with the enhancer core sequence were identified in introns and the 3'-flanking region. Unusual tandem repeats of a sequence, TTTTG, were also found in the 5'-flanking region and introns.

Amino Acid Sequence↗
PubMed2002

Sarco(endo)plasmic reticulum Ca2+-ATPase-2 gene: structure and transcriptional regulation of the human gene.

The sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs) belong to a family of active calcium transport enzymes encoded by the SERCA1, 2, and 3 genes. In this study, we describe the complete structure of the human SERCA2 gene and its 5 -regulatory region. The hSERCA2 gene is located in chromosome 12 position q24.1 in Contig NT_009770.8, spans 70 kb, and is organized in 21 exons intervened by 20 introns. The last two exons of the pre-mRNA produce by alternatively splicing the cardiac/slow-twitch muscle-specific SERCA2a isoform and the ubiquitous SERCA2b isoform. The sequence of the proximal 225-bp regulatory region of the SERCA2 genes is 80% G+C-rich and is conserved among human, rabbit, rat, and mouse species. It contains a TATA-like-box, an E-box/USF sequence, a CAAT-box, four Sp1 binding sites, and a thyroid hormone responsive element (TRE). There are two other conserved regulatory regions located between positions -410 to -661 bp and from -919 to -1410 bp. Among the DNA cis-elements present in these two regulatory regions there are potential binding sites for: GATA-4, -5, -6, Nkx-2.5/Csx, OTF-1, USF, MEF-2, SRF, PPAR/RXR, AP-2, and TREs. Upstream from position -1.5 kb, there is no significant homology among the SERCA2 genes cloned. In addition, the human gene has several repeated sequences mainly of the Alu and L2 type located upstream from position -1.7 kb, spanning in a continuous fashion for more than 40 kb. In this study, we report the cloning of 2.4 kb of 5-regulatory region and demonstrate that the proximal promoter region is sufficient for expression in cardiac myocytes, and the region from -225 to -1232 bp contains regulatory DNA elements which down-regulate the expression of the SERCA2 gene in neonatal cardiomyocytes.

Alternative Splicing↗
PubMed2001

Transposable B2 SINE elements can provide mobile RNA polymerase II promoters.

Short interspersed elements (SINEs) are highly abundant components of mammalian genomes that are propagated by retrotransposition. SINEs are recognized as a causal agent of human disease and must also have had a profound influence in shaping eukaryotic genomes. The B2 SINE family constitutes approximately 0.7% of total mouse genomic DNA (ref. 2) and is also found at low abundance in humans. It resembles the Alu family in several respects, such as its mechanism of propagation. B2 SINEs are derived from tRNA and are transcribed by RNA polymerase (pol) III to generate short transcripts that are not translated. We find here, however, that one B2 SINE also carries an active pol II promoter located outside the tRNA region. Indeed, a B2 element is responsible for the production of a mouse Lama3 transcript. The B2 pol II promoters can be bound and stimulated by the transcription factor USF (for upstream stimulatory factor), as shown by transient transfection experiments. Moreover, this pol II activity does not preclude the pol III transcription necessary for retrotransposition. Dispersal of B2 SINEs by retrotransposition may therefore have provided numerous opportunities for creating regulated pol II transcription at novel genomic sites. This mechanism may have allowed the evolution of new transcription units and new genes.

Animals↗
PubMed1993

Identification and characterization of an Alu-containing, T-cell-specific enhancer located in the last intron of the human CD8 alpha gene.

Expression of the human CD8 alpha gene is restricted to cells of the lymphoid lineage and developmentally regulated during thymopoiesis. As an initial step towards understanding the molecular basis for tissue-specific expression of this gene, we surveyed the surrounding chromatin structure for potential cis-acting regulatory regions by DNase I hypersensitivity mapping and found four hypersensitive sites, three of which were T cell restricted. By using a reporter-based expression approach, a T-cell-specific enhancer was identified by its close association with a prominent T-cell-restricted hypersensitive sites in the last intron of the CD8 alpha gene. Deletion studies demonstrated that the minimal enhancer is adjacent to a negative regulatory element. DNA sequence analysis of the minimal enhancer revealed a striking cluster of consensus binding sites for Ets-1, TCF-1, CRE, GATA-3, LyF-1, and bHLH proteins which were verified by electrophoretic mobility shift assays. In addition, the 5' end of the enhancer was composed of an Alu repeat which contained the GATA-3, bHLH, and LyF-1 binding sites. Site-directed mutation of the Ets-1 and GATA-3 sites dramatically reduced enhancer activity. The functional importance of the other binding sites only became apparent when combinations of mutations were analyzed. Taken together, these results suggest that the human CD8 alpha gene is regulated by the interaction of multiple T-cell nuclear proteins with a transcriptional enhancer located in the last intron of the gene. Comparison of the CD8 alpha enhancer with other recently identified T-cell-specific regulatory elements suggests that a common set of transcription factors regulates several T-cell genes.

Antigens, CD↗
PubMed1988

Isolation and characterization of the bovine kappa-casein gene.

1. The bovine kappa-casein gene has been isolated as a series of overlapping lambda clones and shown to consist of five exons distributed over a total length of approximately 13 kb. Most of the mature protein-coding sequence is contained in a single large exon. 2. Approximately 65% of the gene has been sequenced together with portions of the 5'- and 3'-flanking sequences. The immediate 5'-flanking sequence contains several motifs which are characteristic of upstream regions including a TATA box, a CAAT box, a sequence similar to that recognized by transcription factor AP-1 and a purine-rich sequence resembling that found upstream in all other lactoprotein genes. Other possible regulatory sequences are found upstream of exon 4. 3. The organization of the kappa-casein gene, together with its upstream sequence, confirms previous conclusions that it is unrelated to the calcium-sensitive-casein gene family to which it is linked. Evidence is presented which supports a previous suggestion that kappa-casein and the fibrinogens are evolutionarily related. 4. Intron sequences contain several examples of the A family of the artiodactyl Alu-like repeated sequences, together with a single example of a C-family sequence. The remainders of the introns of the kappa-casein gene, compared with the repeat elements and exons, are A + T-rich. 5. Among the lambda clones isolated, representatives were found of the A and B genetic variants which can be distinguished by restriction-enzyme analysis. Several other examples of polymorphisms in the non-coding region were found.

Alleles↗
PubMed1989

Human ribosomal DNA: conserved sequence elements in a 4.3-kb region downstream from the transcription unit.

The sequence of 4366 bp of nontranscribed spacer (NTS) human ribosomal DNA (rDNA) located downstream from the 3' end of the transcription unit has been determined. The NTS rDNA is rich in pyrimidine nucleotides (31% T and 30% C) that tend to occur on the coding strand in runs of simple sequence repeats. Other highly repetitive sequence elements are also represented, including tracts of (dA-dC)26 and (dG-dT)29 on the coding strand downstream from the putative termination of transcription. Still farther downstream, two Alu repeat sequences are found. Such sequences are also found in rat DNA at comparable locations, consistent with the possibility of a comparable functional role.

Base Composition↗
PubMed1999

[Molecular analysis of integration sites of the drosophila retrotransposon burdock].

Data on molecular analysis of the insertion sites of nine random copies of burdock retrotransposon are presented. The 12-bp consensus sequence of the insertion sites, YNNUTUTUYAYA (Y-pyrimidine; U-purine), was determined. Homology between the burdock sequence and ribosomal genes was revealed. Three copies of this element were located within the region of ribosomal repeats: one copy in the 18S RNA gene, and two copies in the same intergenic spacer region, in the so-called Alu-repeats of Drosophila, in different copies of ribosomal genes.

Animals↗
PubMed1992

Structure and organization of the human S-adenosylmethionine decarboxylase gene.

Genomic clones for the S-adenosylmethionine (AdoMet) decarboxylase gene were isolated from a human chromosome 6 DNA library. In addition, polymerase chain reaction and specific primers were used to amplify fragments from chromosomal DNA covering exonic regions not found in the screening of DNA libraries with AdoMet decarboxylase cDNA. The gene encompasses at least 22 kilobases of chromosome 6 DNA and comprises nine exons and eight introns, in contrast to the corresponding rat gene that has only eight exons (Pulkka, A., Ihalainen, R., Aatsinki, J., and Pajunen, A. (1991) FEBS Lett. 291, 289-295). Exon-intron junctions in the human and rat AdoMet decarboxylase genes were in identical positions except that exons 6 and 7 of the human gene formed a single exon in the rat gene. Alu-like sequences are present in four introns and the 5'-flanking region of the human gene. The promoter region contains a TATA box adjacent to the cap site; in addition, DNA elements for binding of transcription factors AP-1, AP-2, CREB, SP-1, and multiple steroid receptors are present between position -3,158 and the transcription start site. Two AdoMet decarboxylase promoter-reporter gene constructs with about 170 and 1,500 nucleotides of the 5'-flanking DNA were used in transient expression studies. AdoMet decarboxylase promoter was capable of driving reporter gene expression, but it was less active than the murine ornithine decarboxylase promoter. There are at least three potential polyadenylation signals at the 3'-end of the gene, and utilization of the first two results in the formation of the 2.0- and 3.6-kilobase AdoMet decarboxylase mRNA species present in human tissues and cell lines. AdoMet decarboxylase gene-related sequences were also present in a human X chromosome-specific DNA library. Partial nucleotide sequencing of this DNA revealed a lack of introns present in the gene located on chromosome 6, suggesting that the locus on the X chromosome contains a processed AdoMet decarboxylase pseudogene.

3T3 Cells↗