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Results for “Locus Control Region”

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At least 793 records · Page 44Linked to original sources
PubMed2004

Does looping and clustering in the nucleus regulate gene expression?

There has been considerable interest in the way that chromatin is spatially organised within the cell nucleus and how that may relate to gene expression and its control. New molecular techniques have identified looped chromatin domains at the mammalian beta-globin and the Drosophila hsp70 loci. Looped domains may insulate chromatin from the influence of neighbouring domains, and the bases of loops may also act to concentrate proteins locally within the nucleus. The spatial clustering of sequences from the Drosophila bithorax complex, located in trans, has also been demonstrated. An emerging theme is that bringing DNA and proteins together within a defined sub-region of the nuclear volume facilitates both the activation and the repression of gene expression. Nuclear compartments may also be involved in the post-translational modification of proteins by sumoylation and ubiquitylation.

Animals↗
PubMed2004

Ss-LrpB, a novel Lrp-like regulator of Sulfolobus solfataricus P2, binds cooperatively to three conserved targets in its own control region.

Ss-LrpB, a novel Lrp-like DNA-binding protein from the hyperthermophilic crenarchaeon Sulfolobus solfataricus, was shown to bind cooperatively to three regularly spaced targets in its own control region, with as consensus the 15 bp palindrome 5'-TTGYAW WWWWTRCAA-3'. Binding to the border sites occurred with high affinity; the target in the middle proved to be a low affinity site which is stably bound only when both flanking sites are occupied. Ss-LrpB contacts two major groove segments and the intervening minor groove of each site, all aligned on one face of the helix. The operator shows intrinsic bending and is increasingly deformed upon binding of Ss-LrpB to one, two and three targets. Complex formation relies therefore on DNA conformability, protein-DNA and protein-protein contacts. Mobility-shift assays and in gel footprinting indicate that Ss-LrpB and the transcription factors TATA-box binding protein (TBP) and transcription factor B (TFB) can bind simultaneously to the control region. Based on these findings we present a model for the construction of the higher order nucleoprotein complexes and a hypothesis for the autoregulatory process. The latter is based on the concentration-dependent formation of distinct complexes exhibiting different stoichiometries and conformations, which could positively and negatively affect promoter activity.

Archaeal Proteins↗
PubMed2006

Phylogeography of ground tit (Pseudopodoces humilis) based on mtDNA: evidence of past fragmentation on the Tibetan Plateau.

Pseudopodoces humilis, a long misclassified terrestrial tit, is the only species of parid whose distribution is limited to treeless terrain and endemic to the Tibetan Plateau. We revealed the phylogeographic structure of the species by using mitochondrial control region, as well as comparing morphological characters. The distinct geographic distributions of two major clades suggest spatial and temporal separations that coincide with important climatic and paleogeographic changes following the uplift of the Tibetan Plateau. Population expansion was inferred for the population at the platform of the Plateau 0.17 million years before present (Ma B.P.), and restricted gene flow with isolation by distance was detected within this region, congruent with expansion occurring after the extensive glacial period. A significant decrease in body size with decreasing altitude was found, possibly indicating selection for larger-sized birds at higher altitude.

Animals↗
PubMed2005

Unexpected ceiling of genetic differentiation in the control region of the mitochondrial DNA between different subspecies of the ayu Plecoglossus altivelis.

Sequence analyses of the non-coding, control region (CR) and coding region of the ND4-tRNA(Ser) genes in the mitochondrial DNA (mtDNA) were conducted for populations of the ayu Plecoglossus altivelis altivelis and the Ryukyu-ayu P. a. ryukyuensis. The level of genetic differentiation between the two subspecies evaluated from the CR data was substantially low, when comparing with that estimated from ND4-tRNA(Ser) gene region data, as well as those from nuclear genome data sets. By contrast, the differentiation between subspecies in the ND4-tRNA(Ser) gene region was substantial, being consistent with the results from the previous nuclear genome analyses. Results of UPGMA and minimum spanning network analyses also implied the unexpected ceiling of genetic differentiation in the CR. These results suggest that the CR does not reflect accurately the level of overall genetic differentiation between the populations of the ayu, but other coding regions of the mtDNA do reflect it so that the mtDNA on the whole may function as a rich source of useful markers for genetic assessment of populations of this species.

Animals↗
PubMed2000

Functional gene expression domains: defining the functional unit of eukaryotic gene regulation.

The term functional domain is often used to describe the region containing the cis acting sequences that regulate a gene locus. "Strong" domain models propose that the domain is a spatially isolated entity consisting of a region of extended accessible chromatin bordered by insulators that have evolved to act as functional boundaries. However, the observation that independently regulated loci can overlap partially or completely raises questions about functional requirements for physically isolated domain structures. An alternative model, the "weak" domain model, proposes that domain structure is determined by the distribution of binding sites for positively acting factors, without a requirement for functional boundaries. The domain would effectively be the region that contains these factor-binding sites. Specificity of promoter-enhancer interactions would play a major role in maintaining the functional autonomy of adjacent genes. Sequences that interfere with these interactions (frequently characterised as insulators) would be selected against if they occurred within the domain but not at the edges, or in the interdomain regions. As a result, insulators would often be found near the borders of domains without necessarily being selected to act as boundaries.

Animals↗
PubMed1998

Expression-dependent perturbation of nucleosomal phases at HS2 of the human beta-LCR: possible correlation with periodic bent DNA.

DNA bend sites appear periodically at average intervals of 680 bp, corresponding to a length of four nucleosomes, in the human epsilon-, beta- and Ggamma-Agamma-psibeta-globin gene regions. We found that the HS2 region flanked by two DNA bend sites accommodated five nucleosomes and they were regularly phased throughout the region with the exception of that located in the middle, which corresponded to the precise location of HS2 and included the binding site for NF-E2. There appeared to be several phases in this region in the reconstituted chromatin and in erythroid K562 cells where the globin genes are expressed, whereas only one phase was adopted in non-erythroid HeLa cells. Meanwhile, almost unique phases were adopted at the flanking bend sites in vitro as well as in vivo. Sequences of 30 bp containing the bend centers cloned into the vector alone showed identical nucleosomal phases to those observed with the in vitro and in vivo experiments and removing the bend sites caused disruption of the phases at the bend sites as well as those in their direct vicinity. Finally, the nucleosome in this HS2 region had an inhibitory effect on NF-E2 binding, although remodeling occurred with the nuclear extract from K562 cells in the presence of ATP. This suggests that HS2 is placed at a region of weak nucleosome phasing activity along with factor binding sites.

Base Sequence↗
PubMed2006

Comparative phylogeography of the Atlantic forest endemic sloth (Bradypus torquatus) and the widespread three-toed sloth (Bradypus variegatus) (Bradypodidae, Xenarthra).

The comparative phylogeographic study of the maned sloth (Bradypus torquatus) and the three-toed sloth (Bradypus variegatus) was performed using a segment of mitochondrial DNA (mtDNA) control region. We examined 19 B. torquatus from two regions and 47 B. variegatus from three distant regions of Atlantic forest. This first characterization of molecular diversity indicates a great diversity (B. torquatus: h = 0.901 +/- 0.039 and pi = 0.012 +/- 0.007; B. variegatus: h = 0.699 +/- 0.039 and pi = 0.010 +/- 0.006) and very divergent mitochondrial lineages within each sloth species. The different sampled regions carry distinct and non-overlapping sets of mtDNA haplotypes and are genetically divergent. This phylogeographic pattern may be characteristic of sloth species. In addition, we infer that two main phylogeographic groups exist in the Atlantic forest representing a north and south distinct divergence.

Animals↗
PubMed2001

Structure and evolution of the mitochondrial DNA complete control region in the Drosophila subobscura subgroup.

The complete A + T-rich region of mitochondrial DNA (mtDNA) has been cloned and sequenced in the species of the Drosophila subobscura subgroup D. subobscura, D. madeirensis and D. guanche. Comparative analysis of these sequences with others already published has identified new sequence motifs that are conserved in Drosophila and other insects. A putative bi-directional promoter and a stop signal are proposed to be involved in the primary mtDNA strand replication of Drosophila. This region strongly resolves relationships of the species included in a phylogenetic analysis, both for closely related species and also at deeper phylogenetic levels when only the left and central domains are taken into account.

AT Rich Sequence↗
PubMed1998

Population structure of African buffalo inferred from mtDNA sequences and microsatellite loci: high variation but low differentiation.

The African buffalo (Syncerus caffer) is widespread throughout sub-Saharan Africa and is found in most major vegetation types, wherever permanent sources of water are available, making it physically able to disperse through a wide range of habitats. Despite this, the buffalo has been assumed to be strongly philopatric and to form large aggregations that remain within separate home ranges with little interchange between units, but the level of differentiation within the species is unknown. Genetic differences between populations were assessed using mitochondrial DNA (control region) sequence data and analysis of variation at six microsatellite loci among 11 localities in eastern and southern Africa. High levels of genetic variability were found, suggesting that reported severe population bottlenecks due to outbreak of rinderpest during the last century did not strongly reduce the genetic variability within the species. The high level of genetic variation within the species was found to be evenly distributed among populations and only at the continental level were we able to consistently detect significant differentiation, contrasting with the assumed philopatric behaviour of the buffalo. Results of mtDNA and microsatellite data were found to be congruent, disagreeing with the alleged male-biased dispersal. We propose that the observed pattern of the distribution of genetic variation between buffalo populations at the regional level can be caused by fragmentation of a previous panmictic population due to human activity, and at the continental level, reflects an effect of geographical distance between populations.

Animals↗
PubMed1999

Position-dependent inhibition of class-switch recombination by PGK-neor cassettes inserted into the immunoglobulin heavy chain constant region locus.

The Ig heavy chain (IgH) constant region (CH) genes are organized from 5' to 3' in the order Cmicro, Cdelta, Cgamma3, Cgamma1, Cgamma2b, Cgamma2a, Cepsilon, and Calpha. Expression of CH genes downstream of Cdelta involves class-switch recombination (CSR), a process that is targeted by germ-line transcription (GT) of the corresponding CH gene. Previously, we demonstrated that insertion of a PGK-neor cassette at two sites downstream of Calpha inhibits, in cultured B cells, GT of and CSR to a subset of CH genes (including Cgamma3, Cgamma2a, Cgamma2b, and Cepsilon) that lie as far as 120 kb upstream. Here we show that insertion of the PGK-neor cassette in place of sequences in the Igamma2b locus inhibits GT of and CSR to the upstream Cgamma3 gene, but has no major effect on the downstream Cgamma2a and Cepsilon genes. Moreover, replacement of the Cepsilon exons with a PGK-neor cassette in the opposite transcriptional orientation also inhibits, in culture, GT of and CSR to the upstream Cgamma3, Cgamma2b, and Cgamma2a genes. As with the PGK-neor insertions 3' of Calpha studied previously, the Cgamma1 and Calpha genes were less affected by these mutations both in culture and in mice, whereas the Cgamma2b gene appeared less affected in vivo. Our findings support the existence of a long-range 3' IgH regulatory region required for GT of and CSR to multiple CH genes and suggest that PGK-neor cassette insertion into the locus short circuits the ability of this region to facilitate GT of dependent CH genes upstream of the insertion.

Animals↗
PubMed2005

The influence of Pleistocene glacial refugia on tawny owl genetic diversity and phylogeography in western Europe.

The glacial refugia hypothesis indicates that during the height of the Pleistocene glaciations the temperate species that are today widespread in western Europe must have survived in small and climatically favourable areas located in the southern peninsulas of Iberia, Italy and Balkans. One such species is the tawny owl, a relatively sedentary, nonmigratory bird presently distributed throughout Europe. It is a tree-nesting species closely associated with deciduous and mixed coniferous woodlands. In this study I used control region mtDNA sequences from 187 individuals distributed among 14 populations to determine whether current genetic patterns in tawny owl populations were consistent with postglacial expansion from peninsular refugia. European, North African and Asian tawny owls were found to represent three distinct lineages, where North Africa is the sister clade to all European owls. Within Europe, I found three well-supported clades that correspond to each of the three allopatric refugia. Expansion patterns indicate that owls from the Balkan refugium repopulated most of northern Europe, while expansion out of Iberia and Italy had only regional effects leading to admixture in France. Estimates of population divergence times between refugia populations are roughly similar, but one order of magnitude smaller between Greece and northern Europe. Based on a wide range of mutation rates and generation times, divergence between refugia appears to date to the Pleistocene.

Africa, Northern↗
PubMed2000

Intergenic transcription and developmental remodeling of chromatin subdomains in the human beta-globin locus.

Gene activation requires chromatin remodeling complexes, which hyperacetylate histones and enable factor access; however, the targeting mechanisms leading to the establishment and maintenance of large, hyperacetylated DNase-sensitive chromatin domains are unknown. Recent work has shown that histone acetyltransferases are associated with RNA-pol II complexes, suggesting that transcription of chromatin plays a role in chromatin modification. Here we show the human beta-globin locus is divided into three differentially activated chromatin subdomains. Large transcripts precisely delineate the active domains at key cell cycle points associated with chromatin transitions and remodeling. We identify an element that initiates these transcripts, located in a region required for chromatin activation. The results suggest that intergenic transcription is required for chromatin remodeling of chromosomal domains.

Acetyltransferases↗
PubMed2006

SATB1 packages densely looped, transcriptionally active chromatin for coordinated expression of cytokine genes.

SATB1 (special AT-rich sequence binding protein 1) organizes cell type-specific nuclear architecture by anchoring specialized DNA sequences and recruiting chromatin remodeling factors to control gene transcription. We studied the role of SATB1 in regulating the coordinated expression of Il5, Il4 and Il13, located in the 200-kb T-helper 2 (T(H)2) cytokine locus on mouse chromosome 11. We show that on T(H)2 cell activation, SATB1 expression is rapidly induced to form a unique transcriptionally active chromatin structure at the cytokine locus. In this structure, chromatin is folded into numerous small loops, all anchored to SATB1 at their base. In addition, histone H3 is acetylated at Lys9 and Lys14, and the T(H)2-specific factors GATA3, STAT6 and c-Maf, the chromatin-remodeling enzyme Brg1 and RNA polymerase II are all bound across the 200-kb region. Before activation, the T(H)2 cytokine locus is already associated with GATA3 and STAT6, showing some looping, but these are insufficient to induce cytokine gene expression. Using RNA interference, we show that on cell activation, SATB1 is required not only for compacting chromatin into dense loops at the 200-kb cytokine locus but also for inducing Il4, Il5, Il13 and c-Maf expression. Thus, SATB1 is a necessary determinant for the hitherto unidentified higher-order, transcriptionally active chromatin structure that forms on T(H)2 cell activation.

Acetylation↗
PubMed2005

Phylogenetic analysis of the genus Thymallus (grayling) based on mtDNA control region and ATPase 6 genes, with inferences on control region constraints and broad-scale Eurasian phylogeography.

We present first insights into the molecular phylogeny of the grayling genus Thymallus (Salmonidae) using sequences from the mitochondrial control region and ATPase6 genes. A suite of analytical approaches were applied for each gene separately and for the combined data. The ATPase6 gene is shown to have a mean divergence rate across the genus of 2.46 times faster than the complete control region. Based on the combined data, four major (internal) clades, presumably originating in the Pliocene, were resolved with high support in all analyses and represented two distinct lineages in the Amur basin, one lineage in all remaining Siberian and Mongolian drainages, and one lineage corresponding to European grayling Thymallus thymallus. The resolution of multiple lineages, from both additional internal and terminal clades, within each major drainage basin underscores the complexity and effects that Pleistocene hydrological dynamics have had on the distribution of biodiversity in Siberia.

Animals↗
PubMed2006

East Asian mtDNA haplogroup determination in Koreans: haplogroup-level coding region SNP analysis and subhaplogroup-level control region sequence analysis.

The present study analyzed 21 coding region SNP markers and one deletion motif for the determination of East Asian mitochondrial DNA (mtDNA) haplogroups by designing three multiplex systems which apply single base extension methods. Using two multiplex systems, all 593 Korean mtDNAs were allocated into 15 haplogroups: M, D, D4, D5, G, M7, M8, M9, M10, M11, R, R9, B, A, and N9. As the D4 haplotypes occurred most frequently in Koreans, the third multiplex system was used to further define D4 subhaplogroups: D4a, D4b, D4e, D4g, D4h, and D4j. This method allowed the complementation of coding region information with control region mutation motifs and the resultant findings also suggest reliable control region mutation motifs for the assignment of East Asian mtDNA haplogroups. These three multiplex systems produce good results in degraded samples as they contain small PCR products (101-154 bp) for single base extension reactions. SNP scoring was performed in 101 old skeletal remains using these three systems to prove their utility in degraded samples. The sequence analysis of mtDNA control region with high incidence of haplogroup-specific mutations and the selective scoring of highly informative coding region SNPs using the three multiplex systems are useful tools for most applications involving East Asian mtDNA haplogroup determination and haplogroup-directed stringent quality control.

Asian People↗
PubMed2001

Pentanucleotide short tandem repeat locus DXYS156 displays different patterns of variations in human populations.

AIM: To establish a database for the pentameric short tandem repeat locus DXYS156 from worldwide populations for routine genotyping in forensic identity testing and evolutionary biology. METHODS: Using polymerase chain reaction with a newly designed primer pair, we analyzed 1,408 male and female samples from 28 populations representing four major geographic groups. RESULTS: We observed 11 different alleles, which we sequenced and used to construct an allelic ladder. CONCLUSION: DXYS156 displays a contrasting pattern of X-linked and Y-linked variation among geographic regions, and between X and Y chromosomes. This complex allele distribution may be forensically useful for the ethnic differentiation of unknown stains.

Alleles↗
PubMed2005

Ancient mitochondrial M haplogroups identified in the Southwest Pacific.

Based on whole mtDNA sequencing of 14 samples from Northern Island Melanesia, we characterize three formerly unresolved branches of macrohaplogroup M that we call haplogroups M27, M28, and M29. Our 1,399 mtDNA control region sequences and a literature search indicate these haplogroups have extremely limited geographical distributions. Their coding region variation suggests diversification times older than the estimated date for the initial settlement of Northern Island Melanesia. This finding indicates that they were among the earliest mtDNA variants to appear in these islands or in the ancient continent of Sahul. These haplogroups from Northern Island Melanesia extend the existing schema for macrohaplogroup M, with many independent branches distributed across Asia, East Africa, Australia, and Near Oceania.

Ancient Lands↗
PubMed2004

Twinkle and POLG defects enhance age-dependent accumulation of mutations in the control region of mtDNA.

Autosomal dominant and/or recessive progressive external ophthalmoplegia (ad/arPEO) is associated with mtDNA mutagenesis. It can be caused by mutations in three nuclear genes, encoding the adenine nucleotide translocator 1, the mitochondrial helicase Twinkle or DNA polymerase gamma (POLG). How mutations in these genes result in progressive accumulation of multiple mtDNA deletions in post- mitotic tissues is still unclear. A recent hypothesis suggested that mtDNA replication infidelity could promote slipped mispairing, thereby stimulating deletion formation. This hypothesis predicts that mtDNA of ad/arPEO patients will contain frequent mutations throughout; in fact, our analysis of muscle from ad/arPEO patients revealed an age-dependent, enhanced accumulation of point mutations in addition to deletions, but specifically in the mtDNA control region. Both deleted and non-deleted mtDNA molecules showed increased point mutation levels, as did mtDNAs of patients with a single mtDNA deletion, suggesting that point mutations do not cause multiple deletions. Deletion breakpoint analysis showed frequent breakpoints around homopolymeric runs, which could be a signature of replication stalling. Therefore, we propose replication stalling as the principal cause of deletion formation.

Adult↗