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Results for “Locus Control Region”

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PubMed2000

A sequence-ready PAC contig of a 550-kb region on rat chromosome 4 including the diabetes susceptibility gene Lyp.

The Lyp locus controls diabetes development in rats. The diabetogenic allele in diabetes-prone BB rats is responsible for T cell lymphopenia characterized by the absence of regulatory T cells. We present refined genetic and radiation hybrid maps of the Lyp region on rat chromosome 4, a single 800-kb rat yeast artificial chromosome and a rat P1-derived artificial chromosome (PAC) contig corresponding to approximately 550 kb, both encompassing the entire candidate region. The contig, consisting of 48 PACs, gives 3- to 12-fold coverage. Genetic, radiation hybrid, and physical data were all in agreement and supported the same marker order. Nine genes and ESTs were identified in the contig in addition to a rat EST from the University of Iowa rat EST database-all possible candidate genes for Lyp. Alignment of our rat PAC contig with sequenced human PAC/BAC contigs confirms the position within the region of 3 of the 10 candidates and identifies an additional 8 genes/ESTs as candidates. These data will facilitate identification of Lyp.

Animals↗
PubMed2005

Psychological characteristics of cancer patients who use complementary therapies.

There has been considerable research on the prevalence and demographic profile of cancer patients who opt to supplement conventional therapies with the use of complementary therapy. There is rather less information on the personality and adjustment variables associated with the decision to use complementary therapy. The aim of the present study is to investigate the relationship between the use of complementary therapies by cancer patients and their mental adjustment to cancer, recovery locus of control, life orientation and psychopathology. Two groups were drawn from a regional centre which provides both conventional and complementary cancer treatments. Participants in Group 1 (n = 61) opted for complementary therapies in addition to conventional treatments for cancer, while participants in Group 2 (n = 56), chose conventional treatment only. All participants completed the Mental Adjustment to Cancer Scale (MAC), the Recovery Locus of Control Scale (RLOC), the life orientation test (LOT), and the Hospital Anxiety and Depression Scale (HADS). Information regarding demographic details and patients' motivation for the use of complementary therapy was also collected. Those people who chose complementary therapy demonstrated a mental adjustment to cancer which is characterised by significantly higher levels of fighting spirit and anxious preoccupation. This group had also a higher internal recovery locus of control than those receiving conventional treatment alone. There were no significant differences between the groups on life orientation or psychopathology. The findings of this study do not support the argument that the use of complementary therapy is associated with higher levels of psychopathology and distress. However, the data do indicate that for some patients the use of complementary therapy fulfils an important psychological need. The finding that psychosocial variables like fighting spirit and locus of control may impact on an individual's therapeutic choice can assist clinicians in tailoring interventions to personality and adjustment characteristics.

Adaptation, Psychological↗
PubMed1975

The major histocompatibility complex of the guinea pig. I. Serologic and genetic studies.

Serologic and genetic studies of the antigens which comprise the guinea pig MHC have demonstrated three distinct but linked genetic regions. Antisera to the B region were raised by cross-immunization of random-bred animals; this region controls antigens B.1, B.2, B.3, and B.4 which behave as alleles at a single locus and which resemble the products of the murine D or K region genes in their tissue distribution and molecular characteristics. Cross-immunization of inbred strain 2 and strain 13 animals, both of which bear the B.1 antigen, leads to sera which identify antigens which resemble the products of the I region of the murine MHC. Specific absorption experiments have demonstrated four distinct I region antigens. In addition to the B and I regions, inbred strain 2, strain 13, and some outbred animals bear an antigen (S.1) which is the product of a third genetic region and which also resembles the murine D or K region gene products in molecular size. The results of these studies should facilitate the use of the guinea pig as an experimental model for studies of genetic control of the immune response and the function of the histocompatibility-linked Ir genes.

Animals↗
PubMed2000

A novel epigenetic control operating on Vme1+ locus leads to variegated monoallelic expression.

Vme1, located near an imprinted region containing Peg1/Mest, Copg2, and Mit1/Lb9 on mouse chromosome 6, was identified and characterized to be under novel epigenetic regulations mediating nonimprinted monoallelic expression. The gene was transcribed independently from at least four promoters and alternatively spliced. Variable expression of the gene was found among individuals and was not affected by genetic backgrounds, in contrast to a relatively consistent expression of unlinked Peg3 under different genetic backgrounds. Monoallelic expression of the gene was confirmed in several tissues of hybrid F1s between a domesticus and a molossinus subspecies. The nature of monoallelic expression was different from those of its neighboring genes with respect to the allelic preference for the expression. The observed variable expression and monoallelic expression propose a mechanism that operates to variegate the Vme1 transcription acting asynchronously on parental alleles. In addition, we observed that some biallelically expressed tissues exhibited allele-specific splicing such that expression from one parental allele yields elongated splice variants, whereas the other allele is spliced into a short version. This unusual finding suggests that an epigenotype of the promoter can determine the splicing fate of the transcript.

Alleles↗
PubMed1976

Effects of dopamine-receptor blockade on self-stimulation in the monkey.

In a dose-response experiment it was shown that intraperitoneal injections of 0.062 mg/kg, and 0.1 mg/kg of the dopamine-receptor blocking agent and neuroleptic spiroperidol severely attenuate self-stimulation in the orbitofrontal cortex, hypothalamus, and in the region of the locus coeruleus, in the rhesus monkey and in the squirrel monkey. In the rhesus monkey intracranial injections of 6 mug of spiroperidol bilaterally into the nucleus accumbens or the hypothalamus attenuated self-stimulation of the amygdala, and injections into the orbitofrontal cortex attenuated self-stimulation of the amygdala and lateral hypothalamus. Self-stimulation at other sites tested (including the region of the locus coeruleus) was much less affected by the injections, and injections into the region of the locus coeruleus were ineffective. These results together with other control experiments suggest that spiroperidol can attenuate self-stimulation in the monkey independently of any motor impairment or sedation produced, and that dopamine receptors in particular brain regions are involved in self-stimulation of particular brain sites.

Animals↗
PubMed1996

Characterization of the promoter region of human steroid sulfatase: a gene which escapes X inactivation.

The human X-linked steroid sulfatase gene (STS) was among the first genes shown to escape X inactivation. At least fourteen genes regulated in this fashion have now been recognized. They are dispersed into several regions of the X chromosome and may be controlled in a locus specific manner. Studies of the promoters of these genes could provide insights into the mechanism of X inactivation, however little information of this nature is currently available. For this reason we examined 5' flanking sequences of the human STS gene for promoter function. Four transcription start sites scattered over a 50bp region were identified. Functional domains of this TATA-less and GC poor promoter were identified by study of a series of terminal and internal deletions. A putative promoter sequence was identified which by itself exhibits little or no basal activity. However when combined with upstream regulatory elements, this segment showed weak but reproducible activity in a CAT (chloramphenicol acetyltransferase) reporter assay. Several regulatory domains acting as enhancers and repressors were subsequently identified. The relationship of this 5' sequence to the ability of the STS gene to escape X-inactivation is discussed.

Arylsulfatases↗
PubMed2003

Chromosomal elements regulate gene activity and chromatin structure of the human serpin gene cluster at 14q32.1.

The human serine protease inhibitor (serpin) gene cluster at 14q32.1 contains a number of genes that are specifically expressed in hepatic cells. Cell-specific enhancers have been identified in several of these genes, but elements involved in locus-wide gene and chromatin control have yet to be defined. To identify regulatory elements in this region, we prepared a series of mutant chromosomal alleles by homologous recombination and transferred the specifically modified human chromosomes to hepatic cells for functional tests. We report that deletion of an 8-kb DNA segment upstream of the human alpha1-antitrypsin gene yields a mutant serpin allele that fails to be activated in hepatic cells. Within this region, a 2.3-kb DNA segment between kb -8.1 and -5.8 contains a previously unrecognized control region that is required not only for serpin gene activation but also for chromatin remodeling of the entire locus.

Alleles↗
PubMed1984

DNA sequence of the white locus of Drosophila melanogaster.

The DNA sequence of the white locus of Drosophila melanogaster is presented. This 14,100 base-pair sequence includes the region of the locus required for wild-type levels of expression and control of expression. We also report the sequence of a complementary DNA clone which established the position of the 3' end of the white RNA on this genomic sequence. The probable exon-intron structure of the gene has been predicted from the DNA sequence of the regions known to be represented in the RNA. The amino acid sequence of the protein which would be produced by translation of this RNA suggests that the white locus gene product may be a membrane protein. The DNA sequence rearrangements associated with seven insertion mutants (white-dominant-zeste-like (wDZL), white-spotted (wsp), white-honey (wh), white-zeste-mottled (wzm), white-apricot (wa), white-buff (wbf) and white-hd81b11 (whd81b11)), one deletion mutant (white-spotted 4 (wsp4)) and one internal duplication mutant (white-ivory (wi)) have been determined and positioned on the wild-type sequence. The positions of these insertions and those of previously characterized insertions associated with six other mutations suggest that some insertions within an intron may still allow the production of correctly spliced RNA, but affect the amount, and correspondingly the expression of the w locus.

Animals↗
PubMed2003

Regulation of capsule biosynthesis in serotype A strains of Pasteurella multocida.

The capsule of Pasteurella multocida serotype A strain ATCC 11039 is composed of hyaluronic acid and is an important virulence factor. Repeated subculturing of certain capsular serotype A strains results in dissociation from a capsulated to a noncapsulated phenotype with a concomitant loss of virulence. Although noncapsulated variants have been thought to arise as a result of mutation, the molecular mechanisms underlying this event are unknown. In this study, we demonstrate that restoration of the capsulated phenotype occurs in vivo subsequent to intraperitoneal inoculation of BALB/c mice with a noncapsulated variant. Moreover, reverse transcription polymerase chain reaction analysis revealed the capsule locus to be under transcriptional control. Cloning and sequencing of a 290-bp fragment within the promoter containing intergenic region of the capsule locus of 11039/iso revealed no significant alterations occurred subsequent to subculturing. These results demonstrate that serotype A P. multocida strain ATCC 11039 regulates capsule expression in response to an unidentified environmental factor(s), thereby providing insights into the molecular mechanisms underlying colonial dissociation.

Animals↗
PubMed1998

Regulation of expression of the human lymphocyte activation gene-3 (LAG-3) molecule, a ligand for MHC class II.

The lymphocyte activation gene-3 (LAG-3), a major histocompatibility complex (MHC) class II ligand evolutionarily related to CD4, is expressed exclusively in activated T and NK lymphocytes and seems to play a role in regulating the evolving immune response. We first determined that surface LAG-3 expression on activated human T cells is upregulated by certain cytokines (IL-2, IL-7, IL-12) and not by others (IL-4, IL-6, IL-10, TNF-alpha, TNF-beta, IFN-gamma). Surface LAG-3 expression correlated with intracellular IFN-gamma production in both CD4+ and CD8+ T-cell subsets. We then analyzed the 5' transcription control sequences of LAG-3. A DNase I hypersensitive site induced in T cells following cellular activation was found in the region including the transcriptional start site, showing that DNA accessibility is a mechanism which restricts LAG-3 expression to activated T cells. Transcription is initiated at three sites. A GC box, 80 base pairs (bp) upstream of the major transcription start site, forms a minimal promoter which is regulated by two upstream regions containing positive and negative regulatory elements with multiple protein binding sites as shown by footprinting analysis. In particular, a GATA/c-Ets motive was identified in a short segment homologous to the mouse CD4 distal enhancer, suggesting that LAG-3, which is embedded in the CD4 locus, may be controlled by some CD4 regulatory elements. Finally, a 100 bp region downstream of the transcription start site was shown to be involved in the cell-specific control of LAG-3 expression. Understanding this highly regulated expression may help to determine the intriguing role of this activation-induced MHC class II ligand.

Antigens, CD↗
PubMed2004

Intergenic regions in the rhoptry associated protein-1 (rap-1) locus promote exogenous gene expression in Babesia bovis.

Members of the Babesiarap-1 gene family are expressed during multiple parasite stages, and are regulated by both transcriptional and post-transcriptional mechanisms. In all Babesia species, tandemly arranged rap-1 gene copies are separated by an intergenic (IG) region that is hypothesized to regulate gene expression. In this study, we tested that hypothesis by determining whether the Babesia bovisrap-1 IG region could promote extra-chromosomal expression of exogenous genes introduced into merozoites by transfection, and whether a tandem arrangement of IG regions similar to the rap-1 locus enhances exogenous gene expression. Initially, electroporation conditions of B. bovis parasites were determined using expression of the reporter luciferase gene. Both B. bovis transfected by electroporation and Escherichia coli transformed with plasmid p40-15-luc containing the luciferase gene under the control of the B. bovisrap-1 IG and 3' flanking regions were able to express luciferase, indicating that the rap-1 IG region contains a functional promoter. The chromosomal organization of the B. bovisrap-1 locus includes two identical rap-1 open reading frames and IG regions in a head to tail orientation. To determine whether this orientation enhanced expression of exogenous genes, plasmid constructs containing two rap-1-IG regions controlling expression of the luc and human dihydrofolate reductase (hdhfr) genes, and oriented either in head to head (pLuc-H-13) or head to tail (pLuc-H-18) arrangement, were compared. The head to tail orientation of the gene cassettes resulted in a significant increase in the level of luciferase as compared to either head to head orientation or a single IG region construct (p40-15-luc). Thus, an organization that mimics the native structure of the rap-1 locus results in enhanced luciferase expression. These results are the first to demonstrate exogenous gene expression in B. bovis after transfection, and to confirm that the B. bovisrap-1 IG region can promote extra-chromosomal gene expression in vivo.

Amino Acid Sequence↗
PubMed1981

New mouse immunoglobulin A heavy chain allotype specificities detected using the hybridoma-derived IgA of I/St mice.

Immunizations of C57BL/6 and A mice with IgA derived from the I/St mouse strain yield alloantisera which detect two allotypic determinants of immunoglobulin A. The two determinants display discrete strain distributions. The first, identified by the alloantiserum C57BL/6 anti-IgA of I/St strain hybridoma ID150, follows the Ighc haplotype, and the second, identified by the alloantiserum A anti-IgA of I/St strain hybridoma ID150, correlates with Ighc and Ighb haplotypes. Absorption with monoclonal IgM, which has the same idiotype as the ID150 IgA clone, removed idiotype-specific antibodies from both alloantisera. The remaining antibodies are directed against determinants associated with the alpha chain constant region, as shown by absorption with monoclonal IgA. By use of recombinant inbred strains of mice and mice congenic at the Igh locus, the loci controlling both C alpha allotypic determinants have been mapped to the Igh region on chromosome 12.

Animals↗
PubMed2001

Characterization of the S-locus region of almond (Prunus dulcis): analysis of a somaclonal mutant and a cosmid contig for an S haplotype.

Almond has a self-incompatibility system that is controlled by an S locus consisting of the S-RNase gene and an unidentified "pollen S gene." An almond cultivar "Jeffries," a somaclonal mutant of "Nonpareil" (S(c)S(d)), has a dysfunctional S(c) haplotype both in pistil and pollen. Immunoblot and genomic Southern blot analyses detected no S(c) haplotype-specific signal in Jeffries. Southern blot showed that Jeffries has an extra copy of the S(d) haplotype. These results indicate that at least two mutations had occurred to generate Jeffries: (1) deletion of the S(c) haplotype and (2) duplication of the S(d) haplotype. To analyze the extent of the deletion in Jeffries and gain insight into the physical limit of the S locus region, approximately 200 kbp of a cosmid contig for the S(c) haplotype was constructed. Genomic Southern blot analyses showed that the deletion in Jeffries extends beyond the region covered by the contig. Most cosmid end probes, except those near the S(c)-RNase gene, cross-hybridized with DNA fragments from different S haplotypes. This suggests that regions away from the S(c)-RNase gene can recombine between different S haplotypes, implying that the cosmid contig extends to the borders of the S locus.

Base Sequence↗
PubMed2000

Chromatin remodeling by the T cell receptor (TCR)-beta gene enhancer during early T cell development: Implications for the control of TCR-beta locus recombination.

Gene targeting studies have shown that T cell receptor (TCR)-beta gene expression and recombination are inhibited after deletion of an enhancer (Ebeta) located at the 3' end of the approximately 500-kb TCR-beta locus. Using knockout mouse models, we have measured, at different regions throughout the TCR-beta locus, the effects of Ebeta deletion on molecular parameters believed to reflect epigenetic changes associated with the control of gene activation, including restriction endonuclease access to chromosomal DNA, germline transcription, DNA methylation, and histone H3 acetylation. Our results demonstrate that, in early developing thymocytes, Ebeta contributes to major chromatin remodeling directed to an approximately 25-kb upstream domain comprised of the Dbeta-Jbeta locus regions. Accordingly, treatment of Ebeta-deleted thymocytes with the histone deacetylase inhibitor trichostatin A relieved the block in TCR-beta gene expression and promoted recombination within the Dbeta-Jbeta loci. Unexpectedly, however, epigenetic processes at distal Vbeta genes on the 5' side of the locus and at the 3' proximal Vbeta14 gene appear to be less dependent on Ebeta, suggesting that Ebeta activity is confined to a discrete region of the TCR-beta locus. These findings have implications with respect to the developmental control of TCR-beta gene recombination, and the process of allelic exclusion at this locus.

3T3 Cells↗
PubMed1997

Location of the first genetic locus, PKDr1, controlling autosomal dominant polycystic kidney disease in Han:SPRD cy/+ rat.

The Han:SPRD cy/+ strain develops a form of slowly progressive disease that appears similar in many respects to that seen in the autosomal dominant polycystic kidney disease (ADPKD) in humans. We have performed a total genome scan in an experimental backcross population derived from affected Han:SPRD cy/+ rat (PKD) and non-affected Wistar Ottawa Karlsburg rat (WOK) using 117 microsatellite markers. The genetic dissection of PKD allowed us to map on rat chromosome 5, a quantitative trait locus (QTL) controlling PKD, kidney mass and plasma urea concentration. The homology region is likely to reside on human chromosome 8. The gene responsible for PKD in Han:SPRD cy/+ rat is neither PKD1, localised on human chromosome 16, nor PKD2, localised on human chromosome 4. Therefore, we propose that this new locus be denoted PKDr1. The detection of the PKDr1 locus and associated QTL should accelerate research into the genetic causes of ADPKD.

Animals↗
PubMed1990

The beta-globin dominant control region: hypersensitive site 2.

The Dominant Control Region (DCR) of the human beta-globin gene locus consists of four strong hypersensitive sites (HSS) upstream of the epsilon-globin gene. Addition of these sites confers copy number dependent expression on the human beta-globin gene in murine erythroleukaemia cells and transgenic mice, at levels comparable with the endogenous mouse globin genes. We have shown previously that a 1.9 kb fragment comprising HSS 2 accounts for 40-50% of the full effect of the DCR. In this paper we describe a deletional analysis of HSS 2. We show that a 225 bp fragment is sufficient to direct high levels of expression of the human beta-globin gene which is copy number dependent and integration site independent. This 225 bp fragment overlaps the major region that is hypersensitive 'in vivo'. DNase I footprinting shows the presence of four binding sites for the erythroid specific protein NF-E1; the three other footprinted regions display a remarkable redundancy of the sequence GGTGG and bind a number of proteins including Sp1 and the CACC box protein. The significance of these results for the regulation of globin gene expression is discussed.

Animals↗
PubMed1993

Regulatory elements in the immunoglobulin kappa locus induce c-myc activation and the promoter shift in Burkitt's lymphoma cells.

In Burkitt's lymphoma cells the proto-oncogene c-myc is constantly juxtaposed through chromosomal translocation to one of the immunoglobulin loci on chromosomes 14, 2 or 22. In the majority of cases the chromosomal breakpoint is localized 3' or 5' of the gene leaving the physiological c-myc transcription unit intact. As a consequence of the translocation the c-myc gene on the translocation chromosome becomes transcriptionally activated in such a manner that the c-myc promoter P1 is more active than promoter P2. In order to define elements involved in c-myc activation through t(2;8) translocation we have studied the expression of constructs consisting of c-myc and different parts of the immunoglobulin kappa locus after stable transfection into Burkitt's lymphoma cells. The c-myc gene under the control of the complete Ig kappa locus containing matrix attachment region, intron enhancer, constant kappa gene and 3' enhancer was strongly activated with predominant usage of promoter P1. Deletion analysis revealed that the intron or 3' enhancers alone activated c-myc to a much lesser extent and with normal promoter usage (P1 < P2). The cooperation of the same regulatory elements is required not only for transcriptional activation and induction of the promoter shift but also for down-regulation of promoter P1 of the translocated c-myc allele by sodium butyrate, another characteristic feature of Burkitt's lymphoma cells. This supports the notion that all elements involved in transcriptional activation and dysregulation of c-myc are contained within the myc-Ig specific minichromosome.

Base Sequence↗
PubMed2002

Simultaneous improvement for four quality traits of Zhenshan 97, an elite parent of hybrid rice, by molecular marker-assisted selection.

"Zhenshan 97" is the female parent of a number of widely used hybrids for rice production in China. However, this line is of poor quality because of a high amylose content (AC), a hard gel consistency (GC) and a low gelatinization temperature (GT), together with a chalky endosperm. It had been determined that the three traits for cooking and eating quality, AC, GC and GT, are controlled by the Waxy locus and/or the tightly linked genomic region. In this study we improved the eating and cooking quality of Zhenshan 97 by introgressing the Waxy gene region from Minghui 63 (wx-MH), a restorer line, that has medium AC, soft GC and high GT. The wx-MH fragment was transferred to Zhenshan 97B by three backcrosses and one selfing, then from Zhenshan 97B to Zhenshan 97A by a cross and a backcross. Molecular marker-assisted selection was applied in the series to select for individuals carrying wx-MH, to identify recombination between the Waxy and flanking markers, and also to recover the genetic background of the recurrent parent. According to the marker genotypes, the improved versions of Zhenshan 97B and Zhenshan 97A, or Zhenshan 97B(wx-MH) and Zhenshan 97A(wx-MH), were the same as the originals except for the Waxy region of less than 6.1 cM in length. The selected lines and their hybrids with Minghui 63, or Shanyou 63(wx-MH), showed a reduced AC and an increased GC and GT, coupled with a reduced grain opacity. Field examinations of agronomic performance revealed that Zhenshan 97B(wx-MH) and Shanyou 63(wx-MH) were essentially the same as the originals except for a significant decrease in grain weight. The simultaneous improvement of AC, GA, GT and opacity, indicated that the Waxy region had major effects on the four quality traits. The improved versions of Zhenshan 97 A and B should be immediately useful in hybrid rice production.

Amylose↗