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1.
Stefanie Beck Holger Schmitt Hiroaki Shizuya Nikolaus Blin P. Gött 《Human genetics》1996,98(2):233-235
A group of small peptides with a typical cysteine-rich domain (termed trefoil motif or P-domain) is abundantly expressed
at mucosal surfaces of specific normal and neoplastic tissues. Their association with the maintenance of surface integrity
was suggested. The first known human trefoil peptide (pS2) was isolated from breast cancer cells (MCF7). Its oestrogen-inducible
gene, and the human homologue to the porcine spasmolytic peptide gene (hSP/SML1) appear synchronously expressed in healthy
stomach mucosa and several carcinomas of the gastrointestinal tract. Both genes were shown to be localised at 21q22.3. A new
trefoil peptide from human intestinal mucosa (hITF/hP1.B) and its gene were described recently. By using suitable oligonucleotide
primers and PCR and isolating large (110–250 kb) genomic recombinants cloned in the bacterial artificial chromosome (BAC)
system, we present a genomic region from chromosome band 21q22.3 cloned in contiguous sequences and encoding all three members
of human P-domain/trefoil peptides proving a physical linkage of all three trefoil peptide genes. Such genomic sequences will
provide useful experimental material for analysis of gene regulation, for gene modification experiments and for establishing
transgenic cells or animals.
Received: 2 January 1996 / Revised: 4 March 1996 相似文献
2.
hSP, the domain-duplicated homolog of pS2 protein, is co-expressed with pS2 in stomach but not in breast carcinoma. 总被引:26,自引:0,他引:26
C Tomasetto M C Rio C Gautier C Wolf M Hareuveni P Chambon R Lathe 《The EMBO journal》1990,9(2):407-414
Approximately 50% of human breast tumors secrete a small cysteine-rich protein, pS2, of unknown function. pS2 protein was recently found to be homologous to a porcine protein with hormonogastric activity, pancreatic spasmolytic polypeptide (PSP), in which the 5-cysteine domain present in pS2 is tandemly duplicated. We have characterized cDNA species encoding PSP and its human and mouse counterparts, hSP and mSP. We show that hSP and pS2 are separately encoded in the genome, and that the two proteins are co-expressed in normal stomach epithelium. However, expression of hSP was not detected in breast tumors. Computer analysis revealed that the pattern of conserved cysteine residues in hSP and pS2, the P domain, is present at the N termini of two other mammalian proteins, intestinal sucrase-isomaltase and lysosomal alpha-glucosidase. 相似文献
3.
Birgit Theisinger Cornelius Welter Karl-Heinz Grzeschik Nikolaus Blin 《Human genetics》1992,89(6):681-682
Summary A human cDNA corresponding to the porcine pancreatic spasmolytic protein (PSP) was isolated, and the recombinant clone was originally termed hSP for human spasmolytic protein. Later, the term SML1 for spasmolysin was suggested for the human gene. This protein shows a remarkable sequence homology to pS2, a protein coded by an estrogen-induced gene isolated from the breast carcinoma cell line MCF-7. Although, at the DNA level, the gene sequences pS2 and hSP/SML1 display insufficient homology for cross-hybridization, their expression in tumor cells occurs with remarkable coordination. The human pS2 gene sequence has been assigned to chromosome 21, and we have therefore attempted to map the hSP/SMLl gene by using cDNA and Southern blotting of genomic DNAs from a panel of human-rodent somatic cell hybrids carrying different complements of human chromosomes. Interestingly, the hSP/SMLl gene is also localized on chromosome 21. 相似文献
4.
The human spasmolytic protein, SML1/hSP, an inhibitor of spasmolytic activity and gastric acid secretion in the pig, has been shown to exhibit homology to the pS2 protein, an estrogen-dependent breast cancer marker. Moreover, SML1/hSP and pS2 are expressed at the same localization in the normal stomach and during healing of the gastrointestinal tract. Here we report the chromosomal localization, obtained by in situ hybridization, of the hSP gene (SML1) to chromosome 21 at 21q22.3. Using pulsed-field gel electrophoresis, we found SML1 to be within 230 kb of the BCEI/pS2 gene. 相似文献
5.
The mouse one P-domain (pS2) and two P-domain (mSP) genes exhibit distinct patterns of expression 总被引:11,自引:2,他引:9
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《The Journal of cell biology》1993,122(1):191-198
We have previously shown that the human pS2 gene, which codes for a secreted peptide of 60 amino acids, is expressed in a number of human carcinomas, including carcinomas of the breast, the pancreas, and the large bowel. Strong pS2 gene expression was also observed in the normal gastric mucosa and in the regenerative tissues surrounding ulcerous lesions of the gastrointestinal tract. A number of pS2 similar peptides, designated as P-domain peptides, have been described, notably the porcine (PSP), murine (mSP), and human (hSP) spasmolytic polypeptides, which correspond to duplicated pS2 proteins. We have now cloned a mouse homolog of the human pS2 cDNA to dispose of an animal model to study the pS2 protein function, which remains unknown at the present time. We show that the mouse putative pS2 protein sequence and the physiological pattern of expression of the mouse pS2 gene are well conserved. The mouse pS2 gene is highly expressed in the stomach mucosa cells, whereas no pS2 gene expression could be detected in the mouse mammary gland, even during postnatal development processes dependent on growth factors or hormones. Using in situ hybridization, we show that although coexpressed in the fundus, the antrum and the antrum-pyloric regions of the stomach, the mouse pS2 and mSP genes exhibit distinct and complementary cellular patterns of expression. 相似文献
6.
Yunfei Chen Hyun S. Lillehoj Chung-Hsin Hsu Susan L. Carpenter S. J. Lamont 《Immunogenetics》1997,45(4):242-248
A 0.7 kilobase (kb) DNA fragment from the 5′ flanking region of a chicken major histocompatibility complex (MHC) class II B gene was cloned into chloramphenicol acetyltransferase (CAT) reporter vectors and was transfected into a chicken macrophage
cell line that expresses a low level of MHC class II antigens. Positive orientation-dependent promoter activity of the chicken
DNA was evident in a reporter construct containing an SV40 enhancer. Deletion analysis of this 0.7 kb DNA fragment revealed
a short fragment in the 3′ end that was crucial for the promoter function and negative regulatory elements (NRE) located further upstream. The conserved MHC class II X and Y boxes did not have a significant effect on promoter activity. Sequence analysis of the 0.7 kb class II B gene upstream region suggests possible involvement of interferon (IFN), E twenty-six specific (ETS)-related proteins, and
other factors in regulating this promoter. A chicken T-cell line culture supernatant increased surface expression of MHC class
II antigens, as well as class II promoter activity, in this macrophage cell line. This first functional characterization of
a chicken MHC class II B gene promoter will aid in understanding the regulatory mechanisms that control the expression of these genes.
Received: 9 July 1996 / Revised: 7 October 1996 相似文献
7.
F. Latif Fuh-Mei Duh S. Bader Yoshitaka Sekido H. Li L. Geil B. Zbar John D. Minna Michael I. Lerman 《Human genetics》1997,99(3):334-341
Recently, human chromosome band 3p21.3 was shown to undergo overlapping homozygous deletions in several small cell lung cancer
lines further defining a putative tumor suppressor gene(s) region. We report the cloning and mutational analysis of a novel
human gene, SKMc15, from the commonly homozygously deleted region in three small cell lung cancer lines (NCI-H1450, NCI-H740,
GLC20). It has 11 exons ranging in size from 50 to 541 bp with an open reading frame of 442 amino acids. The gene covers 7
to 10 kb of genomic DNA; the message of 1.8 to 2 kb is expressed in all analyzed fetal and adult human and mouse tissues including
heart, brain, placenta, lung liver, skeletal muscle, kidney, testis and pancreas and in small cell and non-small cell cancer
lines. The intron/exon boundaries were used to analyze the gene for mutations by exon PCR-SSCP sequencing in 60 small cell
lung cancer cell lines. No loss-of-function mutations were detected. The cDNA sequence has high homology, 75% at the protein
level, to the rat early response gene PC4 and its murine homolog TIS7. In addition, the known partial sequence of the putative
mouse interferon β2 (64 amino acids) gene is highly conserved in PC4/TIS7 (94%) and in SKMc15 (83%) at the amino acid level.
The sequence TAAAT, which is thought to be involved in mRNA degradation, is present in the 3′ UTR of SKMc15 and in the 3′
UTR of PC4 and TIS7 genes.
Received: 28 August 1996 / Revised: 18 October 1996 相似文献
8.
9.
10.
To understand the role of chromatin structure in the expression of the mouse protamine 1, protamine 2, and transition protein
2 genes during spermatogenesis, we have examined the genomic organization of this cluster of ``haploid-specific' genes. As
seen in the human genome, protamine 2, transition protein 2, and approximately 2.8 kb of a CpG island, hereafter called CpG
island-dTP2, were clustered in a small region. Methylation analyses of this region have demonstrated that i) unlike most other
tissue-specific genes, the protamine 1, protamine 2, and transition protein 2 genes were located in a large methylated domain
in round spermatids, the cell type where they are transcribed, ii) the protamine 1 gene was only partially methylated in somatic
cells and in testes from 7-day-old mice, and iii) the approximately 2 kb upstream and downstream of the CpG island-dTP2 were
only partially methylated in somatic tissues. DNase I analysis revealed the presence of at least five strong DNase I hypersensitive
sites over the CpG island-dTP2 in somatic tissues, but not in germ cells, and sequence analysis indicated that the CpG island-dTP2
is homologous to a CpG island located approximately 10.6 kb downstream of the human transition protein 2 gene. Although the
nature of a CpG island-dTP2 and the function of a CpG island-dTP2-containing somatic tissue-specific DNase I hypersensitive
sites in close proximity to the germ cell-specific gene cluster are unclear, the ``open' chromatin structure of the CpG island-dTP2
may be responsible for the partial methylation pattern of the flanking sequences including the transition protein 2 gene in
somatic tissues.
Received: 6 September 1996 / Accepted: 14 January 1997 相似文献
11.
The SNRPN gene is known to be expressed exclusively from the paternal allele and to map to the critical region for the neurobehavioral
disorder, Prader-Willi syndrome (PWS). As a means to investigate the mechanism of imprinting for the SNRPN gene, we have sought
to recapitulate the imprinted expression of the endogenous gene. Using an 85-kb murine Snrpn clone, containing 33 kb of 5′ and 30 kb of 3′ flanking DNA, we obtained two intact transgenic lines. One line, containing
two copies of the Snrpn transgene, recapitulated the imprinted expression pattern of the endogenous locus, whereas the other transgenic line, containing
a single copy, was expressed upon both maternal and paternal inheritance. This suggests that a 6.6-kb region of maternal-specific
DNA methylation that we have identified may be sufficient to confer imprinted expression, but not in a copy-number independent
manner. Finally, we produced five lines of transgenic mice using a 76-kb human SNRPN clone containing 45 kb and 7 kb of 5′
and 3′ flanking DNA, respectively. We found all the lines were expressed upon both maternal and paternal inheritance, regardless
of copy number, suggesting that the imprinting machinery in mouse and human may have diverged.
Received: 11 November 1998 / Accepted: 29 January 1999 相似文献
12.
Human C8 is one of five components (C5b, C6, C7, C8, C9) of the cytolytic C5b-9 complex of complement. It consists of three
nonidentical subunits (C8α, C8β, C8γ), which are encoded in separate genes. Genetic linkage and chromosomal localization studies
previously established that C8α and C8β are closely linked on chromosome 1p32. In this study, clones with inserts containing
genes for both C8α and C8β were isolated from a yeast artificial chromosome (YAC) human genomic DNA library and characterized
in an effort to determine intergenic distance and orientation. One clone with a ∼330-kb insert yielded restriction digest
patterns for C8α and C8β that agreed with those obtained previously from digests of human genomic DNA, thereby confirming
the presence of intact copies of both genes. A second clone with a ∼280-kb insert yielded similar results; however, it was
truncated at the 5′ end of the C8α gene. Restriction digests of both clones were subjected to PFGE and Southern blot analysis
using probes specific for the terminal exons of C8α (exons 1 and 11) and C8β (exons 1 and 12). Results indicate the genes
are physically linked (< 23 kb) and in a 3′– 3′ orientation. This is the same orientation as the ancestrally related C6 and
C7 genes, which are also physically linked on chromosome 5p13.
Received: 8 March 1996 / Revised: 7 May 1996 相似文献
13.
A genomic sequence analysis of the mouse and human microtubule-associated protein tau 总被引:9,自引:0,他引:9
Parvoneh Poorkaj Arnie Kas Ian D'Souza Yang Zhou Quynh Pham Mariam Stone Maynard V. Olson Gerard D. Schellenberg 《Mammalian genome》2001,12(9):700-712
Microtubule associated protein tau (MAPT) encodes the microtubule associated protein tau, the primary component of neurofibrillary
tangles found in Alzheimer's disease and other neurodegenerative disorders. Mutations in the coding and intronic sequences
of MAPT cause autosomal dominant frontotemporal dementia (FTDP-17). MAPT is also a candidate gene for progressive supranuclear
palsy and hereditary dysphagic dementia. A human PAC (201 kb) and a mouse BAC (161 kb) containing the entire MAPT and Mtapt genes, respectively, were identified and sequenced. Comparative DNA sequence analysis revealed over 100 conserved non-repeat
potential cis-acting regulatory sequences in or close to MAPT. Those islands with greater than 67% nucleotide identity range in size from
20 to greater than 1700 nucleotides. Over 90 single nucleotide polymorphisms were identified in MAPT that are candidate susceptibility
alleles for neurodegenerative disease. The 5′ and 3′ flanking genes for MAPT are the corticotrophin-releasing factor receptor
(CRFR) gene and KIAA1267, a gene of unknown function expressed in brain.
Received: 1 April 2001 / Accepted: 20 April 2001 相似文献
14.
Giese A Jude R Kuiper H Raudsepp T Piumi F Schambony A Guérin G Chowdhary BP Distl O Töpfer-Petersen E Leeb T 《Gene》2002,299(1-2):101-109
15.
J M Jeltsch M Roberts C Schatz J M Garnier A M Brown P Chambon 《Nucleic acids research》1987,15(4):1401-1414
16.
Beckers M Gabriëls J van der Maarel S De Vriese A Frants RR Collen D Belayew A 《Gene》2001,264(1):51-57
The human genome contains hundreds of repeats of the 3.3 kb family in regions associated with heterochromatin. We have previously isolated a 3.3 kb-like cDNA encoding a double homeodomain protein (DUX1). Demonstration that the protein was expressed in human rhabdomyosarcoma TE671 cells, and characterization of a homologous promoter suggested that functional DUX genes might be present in 3.3 kb elements. In the present study, we describe two nearly identical 3.3 kb/DUX genes derived from PAC 137F16 (DUX3), and TE671 genomic DNA (DUX5), both mapping to all the acrocentric chromosomes. Their promoters harbor a GC and a TATAA box, and the open reading frame of the intronless structural part encodes two DUX proteins differing by alternative translation initiation. The shorter protein of the DUX5 gene is identical to DUX1. Using a protein truncation test, we could show that these two proteins are encoded by total RNA, but not by poly (A)(+) RNA, from different human tissues and cell lines. Our results indicate that active genes of unusual structure are present in chromosome regions characterized by large amounts of heterochromatic repetitive DNA. 相似文献
17.
18.
Sally H. Cross Victoria H. Clark Martin W. Simmen Wendy A. Bickmore Habib Maroon Cordelia F. Langford Nigel P. Carter Adrian P. Bird 《Mammalian genome》2000,11(5):373-383
CpG islands are found at the 5′ end of approximately 60% of human genes and so are important genomic landmarks. They are
concentrated in early-replicating, highly acetylated gene-rich regions. With respect to CpG island content, human Chrs 18
and 22 are very different from each other: Chr 18 appears to be CpG island poor, whereas Chr 22 appears to be CpG island rich.
We have constructed and validated CpG island libraries from flow-sorted Chrs 18 and 22 and used these to estimate the difference
in number of CpG islands found on these two chromosomes. These libraries contain normalized collections of sequences from
the 5′ end of genes. Clones from the libraries were sequenced and compared with the sequence databases; one third matched
ESTs, thus anchoring these ESTs at the 5′ end of their gene. However, it was striking that many clones either had no match
or matched only existing CpG island clones. This suggests that a significant proportion of 5′ gene sequences are absent from
databases, presumably either because they are difficult to clone or the gene is poorly expressed and/or has a restricted expression
pattern. This point should be taken into consideration if the currently available libraries are those used for the elucidation
of complete, as opposed to partial, gene sequences. The Chr 18 and 22 CpG island libraries are a sequence resource for the
isolation of such 5′ gene sequences from specific human chromosomes.
Received: 15 November 1999 / Accepted: 31 January 2000 相似文献
19.
Transporters associated with antigen processing molecules (TAP1 and TAP2) mediate the transfer of cytosolic peptides into
the lumen of the endoplasmic reticulum for association with newly synthesized class I molecules of the major histocompatibility
complex. Previous molecular and functional analyses of rat and human TAP2 homologues indicated major differences in gene diversification patterns and selectivity of peptides transported. Therefore,
in this study, we analyzed the alleles of the gorilla TAP2 locus to determine whether the pattern of diversification resembled that in either of those two species. Sequence analysis
of the TAP2 cDNAs from gorilla Epstein-Barr virus-transformed B-cell lines revealed four alleles with a genetic distance of less than
1%. The nucleotide substitutions distinguishing the alleles are confined to the 3′ half of the coding region and occur individually
or within two small clusters of variability. Diversification of the locus appears to have resulted from point substitutions
and recombinational events. Evolutionary-rate estimates for the TAP2 gene in gorilla and human closely approximate those observed for other hominoid genes. The amino acid polymorphisms within
the gorilla molecules are distinct from those in the human homologues. The absence of ancestral polymorphisms suggests that
gorilla and human TAP2 genes have not evolved in a trans-species fashion but rather have diversified since the divergence of the lineages.
Received: 3 January 1996 / Revised: 28 March 1996 相似文献
20.
In ribosomal protein S12 mutant or L24 mutant the expression of λN gene was depressed at translational level. To study its
mechanism the λN gene region of λN -lacZ gene fusion was trimmed from its 5′ end to 3′ end with DNA exonuclease III (DNA cxoIII) in order to alter the TIR (translational
initiation region) and the ding region of λN gene. After DNA sequencing 23 species of different λN-lacZ fused genes were obtained.
The β-galactosidase activities of these deletants in ribosomal protein mutant were compared with that in wild type strain.
The result indicated that (i) S12 mutant could affect 305 subunit’s binding to the TIR of λN gene messenger and cause the
difficulty in forming 30s initiation complex and then decrease the efficiency of translational initiation; (ii) in S12 mutant
the coding region of λN gene alw affected the expression λN gene; (iii) in L24 mutant the inhibition of λN gene expression
was not related to translational initiation and the 5′ end of the coding region of λN gene, but related to the 3′ end of λN
gene.
Project supported by the National Natural Science Foundation of China (Grant Nos. 39480014, 39570162) and Chinese Academy
of Sciences. 相似文献