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Regulatory Site (regulatory + site)
Selected AbstractsTHE LOCUS OF EVOLUTION: EVO DEVO AND THE GENETICS OF ADAPTATIONEVOLUTION, Issue 5 2007Hopi E. Hoekstra An important tenet of evolutionary developmental biology ("evo devo") is that adaptive mutations affecting morphology are more likely to occur in the cis -regulatory regions than in the protein-coding regions of genes. This argument rests on two claims: (1) the modular nature of cis -regulatory elements largely frees them from deleterious pleiotropic effects, and (2) a growing body of empirical evidence appears to support the predominant role of gene regulatory change in adaptation, especially morphological adaptation. Here we discuss and critique these assertions. We first show that there is no theoretical or empirical basis for the evo devo contention that adaptations involving morphology evolve by genetic mechanisms different from those involving physiology and other traits. In addition, some forms of protein evolution can avoid the negative consequences of pleiotropy, most notably via gene duplication. In light of evo devo claims, we then examine the substantial data on the genetic basis of adaptation from both genome-wide surveys and single-locus studies. Genomic studies lend little support to the cis -regulatory theory: many of these have detected adaptation in protein-coding regions, including transcription factors, whereas few have examined regulatory regions. Turning to single-locus studies, we note that the most widely cited examples of adaptive cis -regulatory mutations focus on trait loss rather than gain, and none have yet pinpointed an evolved regulatory site. In contrast, there are many studies that have both identified structural mutations and functionally verified their contribution to adaptation and speciation. Neither the theoretical arguments nor the data from nature, then, support the claim for a predominance of cis -regulatory mutations in evolution. Although this claim may be true, it is at best premature. Adaptation and speciation probably proceed through a combination of cis -regulatory and structural mutations, with a substantial contribution of the latter. [source] The crystal structure of pyruvate decarboxylase from Kluyveromyces lactisFEBS JOURNAL, Issue 18 2006Implications for the substrate activation mechanism of this enzyme The crystal structure of pyruvate decarboxylase from Kluyveromyces lactis has been determined to 2.26 Å resolution. Like other yeast enzymes, Kluyveromyces lactis pyruvate decarboxylase is subject to allosteric substrate activation. Binding of substrate at a regulatory site induces catalytic activity. This process is accompanied by conformational changes and subunit rearrangements. In the nonactivated form of the corresponding enzyme from Saccharomyces cerevisiae, all active sites are solvent accessible due to the high flexibility of loop regions 106,113 and 292,301. The binding of the activator pyruvamide arrests these loops. Consequently, two of four active sites become closed. In Kluyveromyces lactis pyruvate decarboxylase, this half-side closed tetramer is present even without any activator. However, one of the loops (residues 105,113), which are flexible in nonactivated Saccharomyces cerevisiae pyruvate decarboxylase, remains flexible. Even though the tetramer assemblies of both enzyme species are different in the absence of activating agents, their substrate activation kinetics are similar. This implies an equilibrium between the open and the half-side closed state of yeast pyruvate decarboxylase tetramers. The completely open enzyme state is favoured for Saccharomyces cerevisiae pyruvate decarboxylase, whereas the half-side closed form is predominant for Kluyveromyces lactis pyruvate decarboxylase. Consequently, the structuring of the flexible loop region 105,113 seems to be the crucial step during the substrate activation process of Kluyveromyces lactis pyruvate decarboxylase. [source] Specialized rules of gene transcription in male germ cells: the CREM paradigm*INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 6 2004Lucia Monaco Summary Specialized transcription complexes that coordinate the differentiation programme of spermatogenesis have been found in germ cells, which display specific differences in the components of the general transcription machinery. The TATA-binding protein family and its associated cofactors, for example, show upregulated expression in testis. In this physiological context, transcriptional control mediated by the activator cAMP response element modulator (CREM) represents an established paradigm. Somatic cell activation by CREM requires its phosphorylation at a unique regulatory site (Ser117) and subsequent interaction with the ubiquitous coactivator CREB-binding protein. In testis, CREM transcriptional activity is controlled through interaction with a tissue-specific partner, activator of CREM in the testis (ACT), which confers a powerful, phosphorylation-independent activation capacity. The function of ACT was found to be regulated by the testis-specific kinesin KIF17b. Here we discuss some aspects of the testis-specific transcription machinery, whose function is essential for the process of spermatogenesis. [source] The cell differentiation protein SpoIIE contains a regulatory site that controls its phosphatase activity in response to asymmetric septationMOLECULAR MICROBIOLOGY, Issue 4 2002Andrea Feucht Summary Starvation induces Bacillus subtilis to initiate a simple, two-cell developmental process that begins with an asymmetric cell division. Activation of the first compartment-specific transcription factor, ,F, is coupled to this morphological event. SpoIIE, a bifunctional protein, is essential for the compartment-specific activation of ,F and also has a morphogenic activity required for asymmetric cell division. SpoIIE consists of three domains: a hydrophobic N-terminal domain, which targets the protein to the membrane; a central domain, involved in oligomerization of SpoIIE and interaction with the cell division protein FtsZ; and a C-terminal domain comprising a PP2C protein phosphatase. Here, we report the isolation of mutations at the very beginning of the central domain of spoIIE, which are capable of activating ,F independently of septum formation. Purified mutant proteins showed the same phosphatase activity as the wild-type protein in vitro. The mutant proteins were fully functional in respect of their localization to sites of asymmetric septation and support of asymmetric division. The data provide strong evidence that the phosphatase domain of SpoIIE is tightly regulated in a way that makes it respond to the formation of the asymmetric septum. [source] Relationship between SP1 polymorphism and osteoporosis in ,-thalassemia major patientsPEDIATRICS INTERNATIONAL, Issue 4 2008Ozlem Guzeloglu-Kayisli Abstract Background: ,-Thalassemia is an autosomal recessive disease characterized by defective ,-globin chain production. Osteoporosis is an important cause of morbidity in patients with ,-thalassemia major. The pathogenesis of reduced bone mineral density (BMD) is multifactorial. A range of genetics factors have been implicated in other populations of patients with osteoporosis. Polymorphism at the Sp1 binding site of the collagen type I A1 (COLIA1) gene is thought to be an important factor in the development of osteoporosis. Methods: Alleles S and s, detected by presence of a G or T nucleotide, respectively in a regulatory site of the COLIA1 gene were investigated in 37 ,-thalassemia major patients with osteoporosis and 92 controls without osteoporosis or osteopenia using polymerase chain reaction,restriction fragment length polymorphism. Results: Fifteen and nine ,-thalassemia major patients displayed SS and Ss genotypes, respectively, whereas 13 were found to have an ss genotype. The mean BMD of the ,-thalassemia major patients with ss genotype was similar to those with the Ss and SS genotypes. In the control group, 77 and 15 subjects had SS and Ss genotypes, respectively, with no ss genotype. Allelic and genotypic distribution in patients were significantly different from controls. Conclusion: Determining base substitutions at the Sp1 binding site on the COLIA1 gene in early years may be important in preventing osteoporosis in children with ,-thalassemia major. [source] Comparison of binding energies of SrcSH2-phosphotyrosyl peptides with structure-based prediction using surface area based empirical parameterizationPROTEIN SCIENCE, Issue 10 2000Denise A. Henriques Abstract The prediction of binding energies from the three-dimensional (3D) structure of a protein,ligand complex is an important goal of biophysics and structural biology. Here, we critically assess the use of empirical, solvent-accessible surface area-based calculations for the prediction of the binding of Src-SH2 domain with a series of tyrosyl phosphopeptides based on the high-affinity ligand from the hamster middle T antigen (hmT), where the residue in the pY+3 position has been changed. Two other peptides based on the C-terminal regulatory site of the Src protein and the platelet-derived growth factor receptor (PDGFR) are also investigated. Here, we take into account the effects of proton linkage on binding, and test five different surface area-based models that include different treatments for the contributions to conformational change and protein solvation. These differences relate to the treatment of conformational flexibility in the peptide ligand and the inclusion of proximal ordered solvent molecules in the surface area calculations. This allowed the calculation of a range of thermodynamic state functions (,Cp, ,S, ,H, and ,G) directly from structure. Comparison with the experimentally derived data shows little agreement for the interaction of SrcSH2 domain and the range of tyrosyl phosphopeptides. Furthermore, the adoption of the different models to treat conformational change and solvation has a dramatic effect on the calculated thermodynamic functions, making the predicted binding energies highly model dependent. While empirical, solvent-accessible surface area based calculations are becoming widely adopted to interpret thermodynamic data, this study highlights potential problems with application and interpretation of this type of approach. There is undoubtedly some agreement between predicted and experimentally determined thermodynamic parameters; however, the tolerance of this approach is not sufficient to make it ubiquitously applicable. [source] Post-translational Regulation of Endothelial Nitric Oxide Synthase (eNOS) by Estrogens in the Rat VaginaTHE JOURNAL OF SEXUAL MEDICINE, Issue 5 2010Biljana Musicki PhD ABSTRACT Introduction., Estrogens control vaginal blood flow during female sexual arousal mostly through nitric oxide (NO). Although vascular effects of estrogens are attributed to an increase in endothelial NO production, the mechanisms of endothelial NO synthase (eNOS) regulation by estrogens in the vagina are largely unknown. Aims., Our hypothesis was that estrogens regulate eNOS post-translationally in the vagina, providing a mechanism to affect NO bioavailability without changes in eNOS protein expression. Methods., We measured eNOS phosphorylation and eNOS interaction with caveolin-1 and heat shock protein 90 (HSP90) in the distal and proximal vagina of female rats at diestrus, 7 days after ovariectomy and 2 days after replacement of ovariectomized rats with estradiol-17, (15 µg). Main Outcome Measures., Molecular mechanisms of eNOS regulation by estrogen in the rat vagina. Results., We localized phospho-eNOS (Ser-1177) immunohistochemically to the endothelium lining blood vessels and vaginal sinusoids. Estrogen withdrawal decreased phosphorylation of eNOS on its positive regulatory site (Ser-1177) and increased eNOS binding to its negative regulator caveolin-1 (without affecting eNOS/HSP90 interaction), and they were both normalized by estradiol replacement. Protein expressions of phosphorylated Akt (protein kinase B) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) were not affected by estrogen status, suggesting that the effect of estrogens on eNOS (Ser-1177) phosphorylation was not mediated by activated AKT or ERK1/2. eNOS phosphorylation on its negative regulatory site (Ser-114) was increased in the vagina by estrogen withdrawal and normalized by estradiol replacement, implying that the maintenance of low phosphorylation of eNOS on this site by estradiol may limit eNOS interaction with caveolin-1 and preserve the enzyme's activity. Total eNOS, inducible NOS, caveolin-1, and HSP90 protein expressions were not affected by ovariectomy or estradiol replacement in the distal or proximal vagina. Conclusions., These results define novel estrogen signaling mechanisms in the vagina which involve eNOS phosphorylation and eNOS,caveolin-1 interaction. Musicki B, Liu T, Strong TD, Lagoda GA, Bivalacqua TJ, and Burnett AL. Post-translational regulation of endothelial nitric oxide synthase (eNOS) by estrogens in the rat vagina. J Sex Med 2010;7:1768,1777. [source] Age-Related Changes in Phosphorylation of Endothelial Nitric Oxide Synthase in the Rat PenisTHE JOURNAL OF SEXUAL MEDICINE, Issue 3 2005Biljana Musicki PhD ABSTRACT Aim., Aging is associated with erectile dysfunction (ED) attributed to reduced nitric oxide synthase (NOS) activity and nitric oxide bioavailability. However, the mechanism for this effect has not been fully investigated. We evaluated (i) whether age-related ED involves dysregulation of endothelial NOS (eNOS) phosphorylation; and (ii) whether vascular endothelial growth factor (VEGF) exerts erectile effects and operates via eNOS phosphorylation in aged rats. Methods., Male Fischer 344 "young" (4-month-old) and "aged" (19-month-old) rats were used. Electrical stimulation of the cavernous nerve (CNS) was performed to generate penile erection. Erectile response in the presence of rhVEGF165 was evaluated by intracavernosal pressure monitoring 25 minutes after intracavernosal injection of VEGF. Penes were excised at baseline, with or without rhVEGF treatment, and after CNS for Western immunoblot of phospho-eNOS (Ser-1177 and Thr-495), phospho-Akt, and eNOS. Results., Erectile response was significantly reduced in aged rats compared with young rats. Phospho-eNOS (Ser-1177) and phospho-Akt were significantly reduced, while phospho-eNOS (Thr-495) was significantly increased, in the aged penis at baseline and after CNS. rhVEGF significantly improved erection and reversed downregulated Ser-1177, but not upregulated Thr-495 phosphorylation, on eNOS in aged penes. eNOS protein was significantly increased in aged penes. Conclusions., Age-related ED is associated with eNOS inactivation through a decrease in phosphorylation of its positive regulatory site (Ser-1177) and an increase in phosphorylation of its negative regulatory site (Thr-495) in the penis. Altered phosphorylation/constitutive activation of eNOS by fluid shear stress may be a major determinant of compromised vascular homeostasis of the aged penis. The finding that VEGF rapidly induces erection and partly corrects alterations in eNOS phosphorylation in the aged rat penis suggests impaired eNOS activation by deficient endogenous VEGF and supports the potential for growth factor therapy in the treatment of age-related ED. [source] Electrophoretic variants of cardiac myosin heavy chain-, in Sprague Dawley ratsELECTROPHORESIS, Issue 3 2004Peter J. Reiser Abstract Analysis of cardiac myosin revealed differences in gel electrophoretic migration patterns of the ,-isoform of myosin heavy chain, but not the ,-isoform, in Sprague Dawley rats. No differences in the migration patterns of the ,-or ,-isoforms were observed in other rat strains. Three electrophoretic migration patterns of the ,-isoforms were observed in individual rats: a slower migrating isoform alone (4% of all rats tested), a faster migrating isoform alone (55%), and both isoforms (41%). The isoform expression pattern was identical in all myocardial regions in each rat. Frequency of expression patterns suggests multiple gene sequences for ,-cardiac myosin heavy chain in Sprague Dawley rats. Sequence analysis of amplified regions of the Sprague Dawley and Brown Norway rat ,-myosin genes, specifically the 5'-untranslated region, exons 1,3, and associated introns, showed numerous single nucleotide polymorphisms in coding and noncoding regions, including putative regulatory sites in Sprague Dawley rats, but not in Brown Norway rats. All Sprague Dawley rats varied from Brown Norway rats and no heterogeneity was observed in Brown Norway rats. Several deletions and dimorphic positions were also observed. Dimorphic positions were evident on automated sequencing comparisons. The data indicate that at least two ,-myosin heavy chain isoforms exist in Sprague Dawley rats and these rats exhibit sequence diversity within that portion of the ,-myosin heavy chain gene reported in this study. [source] Insight into the molecular mechanisms of glucocorticoid receptor action promotes identification of novel ligands with an improved therapeutic indexEXPERIMENTAL DERMATOLOGY, Issue 8 2006Heike Schäcke Abstract:, Glucocorticoids are highly effective in the therapy of inflammatory and autoimmune disorders. Their beneficial action is restricted because of their adverse effects upon prolonged usage. Topical glucocorticoids that act locally have been developed to significantly reduce systemic side effects. Nonetheless, undesirable cutaneous effects such as skin atrophy persist from the use of topical glucocorticoids. There is therefore a high medical need for drugs as effective as glucocorticoids but with a reduced side-effect profile. Glucocorticoids function by binding to and activating the glucocorticoid receptor that positively or negatively regulates the expression of specific genes. Several experiments suggest that the negative regulation of gene expression by the glucocorticoid receptor accounts for its anti-inflammatory action. This occurs through direct or indirect binding of the receptor to transcription factors such as activator protein-1, nuclear factor- ,B or interferon regulatory factor-3 that are already bound to their regulatory sites. The positive action of the receptor occurs through homodimer binding of the receptor to discrete nucleotide sequences and this possibly contributes to some of the adverse effects of the hormone. Glucocorticoid receptor ligands that promote the negative regulatory action of the receptor with reduced positive regulatory function should therefore show improved therapeutic potential. A complete separation of the positive from the negative regulatory activities of the receptor has so far not been possible because of the interdependent nature of the two regulatory processes. Nevertheless, considerable improvement in the therapeutic action of glucocorticoid receptor ligands is being achieved through the use of key molecular targets for screening novel glucocorticoid receptor ligands. [source] Defining ETS transcription regulatory networks and their contribution to breast cancer progressionJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2007David P. Turner Abstract ETS factors are members of one of the largest families of evolutionarily conserved transcription factors, regulating critical functions in normal cell homeostasis, that when perturbed contribute to tumor progression. The well documented alterations in ETS factor expression and function during breast cancer progression result in pleiotropic effects manifested by the downstream effect on their target genes. Multiple ETS factors bind to the same regulatory sites present on target genes, suggesting redundant or competitive functions. Furthermore, additional events contribute to, or may be necessary for, target gene regulation. In order to advance our understanding of the ETS-dependent regulation of breast cancer progression and metastasis, this prospect article puts forward a model for examining the effects of simultaneous expression of multiple transcription factors on the transcriptome of non-metastatic and metastatic breast cancer. Compared to existing RNA profiles defined following expression of individual transcription factors, the anti- and pro-metastatic signatures obtained by examining specific ETS regulatory networks will significantly improve our ability to accurately predict tumor progression and advance our understanding of gene regulation in cancer. Coordination of multiple ETS gene functions also mediates interactions between tumor and stromal cells and thus contributes to the cancer phenotype. As such, these new insights may provide a novel view of the ETS gene family as well as a focal point for studying the complex biological control involved in tumor progression. J. Cell. Biochem. 102: 549,559, 2007. © 2007 Wiley-Liss, Inc. [source] Transcriptional regulation of transport and utilization systems for hexuronides, hexuronates and hexonates in gamma purple bacteriaMOLECULAR MICROBIOLOGY, Issue 4 2000Dmitry A. Rodionov The comparative approach is a powerful tool for the analysis of gene regulation in bacterial genomes. It can be applied to the analysis of regulons that have been studied experimentally as well as that of regulons for which no known regulatory sites are available. It is assumed that the set of co-regulated genes and the regulatory signal itself are conserved in related genomes. Here, we use genomic comparisons to study the regulation of transport and utilization systems for sugar acids in gamma purple bacteria Escherichia coli, Salmonella typhi, Klebsiella pneumoniae, Yersinia pestis, Erwinia chrysanthemi, Haemophilus influenzae and Vibrio cholerae. The variability of the operon structure and the location of the operator sites for the main transcription factors are demonstrated. The common metabolic map is combined with known and predicted regulatory interactions. It includes all known and predicted members of the GntR, UxuR/ExuR, KdgR, UidR and IdnR regulons. Moreover, most members of these regulons seem to be under catabolite repression mediated by CRP. The candidate UxuR/ExuR signal is proposed, the KdgR consensus is extended, and new operators for all transcription factors are identified in all studied genomes. Two new members of the KdgR regulon, a hypothetical ATP-dependent transport system OgtABCD and YjgK protein with unknown function, are detected. The former is likely to be the transport system for the products of pectin degradation, oligogalacturonides. [source] Microscopy reveals disease control through novel effects on fungal development: a case study with an early-generation benzophenone fungicide,PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 5 2006Mark R Schmitt Abstract The benzophenones are a new class of agricultural fungicides that demonstrate protectant, curative and eradicative/antisporulant activity against powdery mildews. The chemistry is represented in the marketplace by the fungicide metrafenone, recently introduced by BASF and discussed in the following paper. The benzophenones show no evidence of acting by previously identified biochemical mechanisms, nor do they show cross-resistance with existing fungicides. The value of microscopy in elucidating fungicide mode of action is demonstrated through identification of the effects of an early benzophenone, eBZO, on mildew development. eBZO caused profound alterations in the morphology of powdery mildews of both monocotyledons and dicotyledons, affecting multiple stages of fungal development, including spore germination, appressorial formation, penetration, surface hyphal morphology and sporogenesis. Identification of analogous effects of eBZO on sporulation in the model organism Aspergillus nidulans (Eidam) Winter provides a unique opportunity to elucidate important morphogenetic regulatory sites in the economically important obligate pathogens, the powdery mildews. Benzophenones provide a further example of the benefits of whole-organism testing in the search for novel fungicide modes of action. Copyright © 2006 Society of Chemical Industry [source] A study of Streptococcus thermophilus proteome by integrated analytical procedures and differential expression investigationsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 1 2006Simona Arena Abstract Streptococcus thermophilus is a Gram-positive bacterium belonging to the group of lactic acid bacteria, among which several genera play an essential role in manufacture of food products. Recently, a genomic consortium sequenced and annotated its entire genome, which has been demonstrated to contain 1900 coding sequences. In this study, we have revealed the expression products of almost 200 different genes using a proteomic strategy combining 2-DE plus MALDI-TOF PMF and differential 1-DE plus ,LC-ESI-IT-MS/MS. Thus, a number of cellular pathways related to important physiological processes were described at the proteomic level. Almost 50 genes were related to multiple electrophoretic species, whose heterogeneity was mainly due to variability in pI values. A 2-DE reference map obtained for lactose-grown cells was compared with those obtained after heat, cold, acid, oxidative and starvation stresses. Protein up/down-regulation measurements demonstrated that adaptation to different environmental challenges may involve the contribution of unique as well as combined physiological mechanisms. Common regulatory sites in the promoter region of genes whose expression was induced after stress were identified. These results provide a better comprehension of biochemical processes related to stress resistance in S. thermophilus, allowing defining the molecular bases of adaptative responses or markers for the identification of strains with potential industrial applications. [source] Ca2+ -dependent inactivation of Ca2+ -induced Ca2+ release in bullfrog sympathetic neuronsTHE JOURNAL OF PHYSIOLOGY, Issue 14 2008Tenpei Akita We studied inactivation of Ca2+ -induced Ca2+ release (CICR) via ryanodine receptors (RyRs) in bullfrog sympathetic neurons. The rate of rise in [Ca2+]i due to CICR evoked by a depolarizing pulse decreased markedly within 10,20 ms to a much slower rate despite persistent Ca2+ entry and little depletion of Ca2+ stores. The Ca2+ entry elicited by the subsequent pulse within 50 ms, during which the [Ca2+]i level remained unchanged, did not generate a distinct [Ca2+]i rise. This mode of [Ca2+]i rise was unaffected by a mitochondrial uncoupler, carbonyl cyanide p -trifluromethoxy-phenylhydrazone (FCCP, 1 ,m). Paired pulses of varying interval and duration revealed that recovery from inactivation became distinct , 50 ms after depolarization and depended on [Ca2+]i. The inactivation was prevented by BAPTA (, 100 ,m) but not by EGTA (, 10 mm), whereas the activation was less affected by BAPTA. When CICR was partially activated, some of the non-activated RyRs were also inactivated directly. Thus, the inactivation in these neurons is induced by Ca2+ binding to the high-affinity regulatory sites residing very close to Ca2+ channels and/or RyRs, although the sites for activation are located much closer to those Ca2+ sources. The rate of [Ca2+]i decay after the pulse decreased with increasing pulse duration longer than 10 ms, and this was abolished by BAPTA. Thus, some mechanism counteracting Ca2+ clearance is induced after full inactivation and potentiated during the pulse. Possible models for RyR inactivation were proposed and the roles of inactivation in Ca2+ signalling were discussed. [source] Common promoter deletion is associated with 3.9-fold differential transcription of ovine CCR5 and reduced proviral level of ovine progressive pneumonia virusANIMAL GENETICS, Issue 5 2009S. N. White Summary Chemokine (C-C motif) Receptor 5 (CCR5) is a chemokine receptor that regulates immune cell recruitment in inflammation and serves as a coreceptor for human immunodeficiency virus (HIV). A human CCR5 coding deletion (termed delta-32) results in strong resistance to HIV infection, and sequence variants in CCR5 regulatory regions have been implicated in delayed progression to acquired immune deficiency syndrome. Both ovine progressive pneumonia virus (OPPV), also known as maedi-visna, and HIV are macrophage-tropic lentiviruses, have similar genomic structures, and cause lifelong persistent host infection, suggesting CCR5 may have a role in regulating OPPV provirus levels. Therefore, the ovine CCR5 genomic sequence was determined, and sequence variants were obtained from the open reading frame and surrounding regulatory sites. One CCR5 variant contained a 4-base deletion within a binding site for octamer transcription factors in the promoter region. A test for differential transcription from each allele in heterozygous animals showed a 3.9-fold transcription difference (P < 0.0001). OPPV proviral levels were also measured in 351 naturally exposed Rambouillet, Polypay and Columbia sheep. Deletion homozygotes showed reduced OPPV proviral levels among these animals (P < 0.01). The association of this CCR5 promoter deletion with OPPV levels will need to be validated in additional populations before the deletion can be recommended for widespread use in marker-assisted selection. However, because of the large impact on transcription and because CCR5 has roles in inflammation, recruitment of effector cells, and cell-mediated immunity, this deletion may play a role in the control of infections of many diverse pathogens of sheep. [source] | ||||||||||||||||