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Pseudoglandular elements in schwannomas.

CONTEXT: Uncommon examples of schwannomas are seen in which a coexisting glandular component is present. The pseudoglandular schwannoma is a relatively recently described variant in which cystic spaces are lined by pseudocolumnar or cuboidal-like neoplastic Schwann cells exhibiting an epithelial-like appearance. OBJECTIVES: To determine the incidence of pseudoglandular elements in schwannomas, to describe the variable morphology of the schwannomas that may contain pseudoglandular elements, and to discuss the potential mechanisms of development and biological significance of these elements. DESIGN: We screened 202 schwannomas from any anatomic site for the presence of pseudoglandular elements and examined these with light microscopy, immunohistochemistry, and electron microscopy. RESULTS: Sixteen (7.9%) of the schwannomas contained pseudoglandular elements, which ranged from poorly to well organized in appearance and which were found in schwannomas exhibiting a wide range of morphologic appearances. The Schwann cell nature of the cells composing these elements was apparent both immunohistochemically and ultrastructurally. The frequency of proliferative activity within these elements was no greater than that observed throughout the remainder of the respective schwannomas. CONCLUSIONS: Our observations suggest that, rather than representing a distinct phenotypic schwannoma variant, pseudoglandular elements likely arise as a response to a degenerative phenomenon, perhaps reflecting the propensity that the Schwann cell has to palisade formation. Such elements may be found within a variety of schwannoma variants and do not appear to possess a unique growth potential.

Biomarkers, Tumor↗

Molecular cloning and phylogenetic analysis of the human endogenous retrovirus HERV-K long terminal repeat elements in various cancer cells.

Long terminal repeats (LTRs) of the human endogenous retroviruses K family (HERV-K) have been found to affect expression of genes located nearby. It has been suggested that the HERV-K LTR elements contributed to the structural change in the genome and genetic variation connected to various diseases. We examined the HERV-K LTR elements in human cancer cells. Using genomic DNA from various cancer cells, we performed PCR amplification and identified forty-nine HERV-K LTR elements. Those LTR elements showed a high degree of sequence similarity with human-specific HERV-K LTR elements. A phylogenetic tree, obtained by the neighbor-joining method, revealed that twelve HERV-K LTR elements were closely related to human-specific HERV-K LTR elements. These elements proliferated recently and were detectable in many human cancer cell lines. These results suggest that HERV-K LTR could be implicated in a pathogenic role, although this phenomenon may not directly lead to human cancers. Further studies on the biological function and expression of HERV-K LTR elements in cancer cells are indicated.

Cloning, Molecular↗

[Comparative studies of the tridosha theory in Ayurveda and the theory of the four deranged elements in Buddhist medicine].

It has been said that the tridosha theory in Ayurveda originated from the theory of the three elements of the universe. The names of these three doshas, which are roughly equivalent to humour, are vata (wind), pitta (bile), and Kapha (phlegm), corresponding to the three elements of the universe: air, fire, and water. On the other hand, Buddhist medicine which has a close relation to Ayurveda is based on the theory of the four elements of the universe which includes the earth as well as the three elements mentioned above. Greek medicine on the other hand, is founded on the theory of the four humours, i.e. blood, yellow bile, black bile, and phlegm. Furthermore, even in Ayurveda, like in "Sushruta Samhita", the theory of the four humours can be found: this includes the above-mentioned tridosha plus blood as the fourth humour. "Timaios" by Plato also mentions this. We compared these various theories and pointed out that the tridosha theory had its origin in the theory of the four elements of the universe. The process of the formation of the tridosha theory is considered as follows: (1) "Earth" was segregated from the four elements of the universe owing to its solid properties, and was rearranged into the seven elements of the body called "dhatu"; and the other three elements. "water", "fire", and "air", were integrated as the tridosha theory, namely, the theory of the three humours, owing to their properties of fluid; (2) "Blood", assigned to the element of "earth", was segregated from the tridosha because "blood" was considered to be comprised of the properties of every humour without having its own peculiar properties. Therefore, the diseases caused by deranged "blood" were regarded as an aggregate disease caused by the other three deranged humours. Then the category of the disease, caused by deranged "earth", did not appear.

Buddhism↗

Finite element methods for the biomechanics of soft hydrated tissues: nonlinear analysis and adaptive control of meshes.

This chapter addresses computationally demanding numerical formulations in the biomechanics of soft tissues. The theory of mixtures can be used to represent soft hydrated tissues in the human musculoskeletal system as a two-phase continuum consisting of an incompressible solid phase (collagen and proteoglycan) and an incompressible fluid phase (interstitial water). We first consider the finite deformation of soft hydrated tissues in which the solid phase is represented as hyperelastic. A finite element formulation of the governing nonlinear biphasic equations is presented based on a mixed-penalty approach and derived using the weighted residual method. Fluid and solid phase deformation, velocity, and pressure are interpolated within each element, and the pressure variables within each element are eliminated at the element level. A system of nonlinear, first-order differential equations in the fluid and solid phase deformation and velocity is obtained. In order to solve these equations, the contributions of the hyperelastic solid phase are incrementally linearized, a finite difference rule is introduced for temporal discretization, and an iterative scheme is adopted to achieve equilibrium at the end of each time increment. We demonstrate the accuracy and adequacy of the procedure using a six-node, isoparametric axisymmetric element, and we present an example problem for which independent numerical solution is available. Next, we present an automated, adaptive environment for the simulation of soft tissue continua in which the finite element analysis is coupled with automatic mesh generation, error indicators, and projection methods. Mesh generation and updating, including both refinement and coarsening, for the two-dimensional examples examined in this study are performed using the finite quadtree approach. The adaptive analysis is based on an error indicator which is the L2 norm of the difference between the finite element solution and a projected finite element solution. Total stress, calculated as the sum of the solid and fluid phase stresses, is used in the error indicator. To allow the finite difference algorithm to proceed in time using an updated mesh, solution values must be transferred to the new nodal locations. This rezoning is accomplished using a projected field for the primary variables. The accuracy and effectiveness of this adaptive finite element analysis is demonstrated using a linear, two-dimensional, axisymmetric problem corresponding to the indentation of a thin sheet of soft tissue. The method is shown to effectively capture the steep gradients and to produce solutions in good agreement with independent, converged, numerical solutions.

Adaptation, Physiological↗

Identification of an estrogen response element in the 3'-flanking region of the murine c-fos protooncogene.

We have used transient transfection assays with reporter plasmids expressing chloramphenicol acetyltransferase, linked to regions of mouse c-fos, to identify a specific estrogen response element (ERE) in this protooncogene. This element is located in the untranslated 3'-flanking region of the c-fos gene, 5 kilobases (kb) downstream from the c-fos promoter and 1.5 kb downstream of the poly(A) signal. This element confers estrogen responsiveness to chloramphenicol acetyltransferase reporters linked to both the herpes simplex virus thymidine kinase promoter and the homologous c-fos promoter. Deletion analysis localized the response element to a 200-base pair fragment which contains the element GGTCACCACAGCC that resembles the consensus ERE sequence GGTCACAGTGACC originally identified in Xenopus vitellogenin A2 gene. A synthetic 36-base pair oligodeoxynucleotide containing this c-fos sequence conferred estrogen inducibility to the thymidine kinase promoter. The corresponding sequence also induced reporter activity when present in the c-fos gene fragment 3 kb from the thymidine kinase promoter. Gel-shift experiments demonstrated that synthetic oligonucleotides containing either the consensus ERE or the c-fos element bind human estrogen receptor obtained from a yeast expression system. However, the mobility of the shifted band is faster for the fos-ERE-complex than the consensus ERE complex suggesting that the three-dimensional structure of the protein-DNA complexes is different or that other factors are differentially involved in the two reactions. When the 5'-GGTCA sequence present in the c-fos ERE is mutated to 5'-TTTCA, transcriptional activation and receptor binding activities are both lost. Mutation of the CAGCC-3' element corresponding to the second half-site of the c-fos sequence also led to the loss of receptor binding activity, suggesting that both half-sites of this element are involved in this function. The estrogen induction mediated by either the c-fos or the consensus ERE was blunted by the antiestrogen tamoxifen. Based on these studies, we believe the 3'-fos ERE sequence we have identified may be a major cis-acting element involved in the physiological regulation of the gene by estrogens in vivo.

Animals↗

Trace elements and the European skeleton through 5000 years.

For our research, one thousand forty-four samples were taken from the femurs of 522 skeletons from 25 sites in Europe from the Neolithic Age (4000-5000 B.C), from La Téne Period, the Roman Era (500 B.C-400 A.D.), the Middle Ages and from contemporary cadavers. We found the following distribution of elements in the longitudional axis of long bones (the femurs and the tibias). The elements Zn, Fe, Ni, Cr, Pb, Mn, Co and Sn cumulated in the epiphysis. On the other hand, we found that Ca, Sr, Na and K prevailed in the central part of the diaphysis. In the central parts of the cross-section the highest concentration of the metal element Pb was in the external layer from the historical femurs. It was the same with cadavers of the recent population. A specific shift from Neolithic farming to agricultural intensification in the Roman Era was also apparent in the skeletons. Special sources of the above mentioned elements were found both in Celtic and Germanic tribes. Meat is the main source of zinc. Zinc is also important for the growth of the skeleton. When we investigated the development of the human skeleton during the last 5000 years we found the highest concetrations of Zn in communities with a good supply of animal food, whereas the lowest concentrations were paralleled with well-developed agriculturists. We assume the Neolithic gracilization, which is in the background for the increase of agricultural populations, is directly linked with the concentration of Zn and other elements essential for growth (Cu, Fe and others). The individuals most vulnerable to zinc deficiency include infants, adolescents during rapid growth phases and women during pregnancy and lactation. Trace elements in the bones of the La Téne period designate two areas of Celtic diet patterns--a "French one" (Roulier, Mont Trote and Acy Romance) and a "Czech one" (Karlov, Radovesice and Jenisův Ujezd). At Czech sites levels of zinc increased westward towards the Germanic region. Over the Germanic territory in the region of the Saala River there are similar supply trace element sources for bones of the Germanic tribes for a period of more than 1000 years. The dietary customs and environment that formed this development were preserved from 400 B.C. to the period of the Merovingians. A specific ratio of Zn and Sr can be found not only in men, but also in woman and children. At the beginning of our era lead emerged as a civilization element. This element influenced the diet until the 20th century. Since the beginning of the 20th century it occurs much less in the population. On the contrary, we have found significant presence of tin in human bones. Cadavers of the modem population indicate a high content of tin, considerably higher than those in the populations from the beginning of our era (as much as 40 microg.g(-1) bone).

Bone and Bones↗

Element cycling in the dominant plant community in the Alpine tundra zone of Changbai Mountains, China.

Element cycling in the dominant plant communities including Rh. aureum, Rh. redowskianum and Vaccinium uliginosum in the Alpine tundra zone of Changbai Mountains in northeast China was studied. The results indicate that the amount of elements from litter decomposition was less than that of the plant uptake from soil, but that from plant uptake was higher than that in soil with mineralization process released. On the other hand, in the open system including precipitation input and soil leaching output, because of great number of elements from precipitation into the open system, the element cycling(except N, P) in the Alpine tundra ecosystem was in a dynamic balance. In this study, it was also found that different organ of plants had significant difference in accumulating elements. Ca, Mg, P and N were accumulated more obviously in leaves, while Fe was in roots. The degree of concentration of elements in different tissues of the same organ of the plants also was different, a higher concentration of Ca, Mg, P and N in mesophyll than in nerve but Fe was in a reversed order. The phenomenon indicates (1) a variety of biochemical functions of different elements, (2) the elements in mesophyll were with a shorter turnover period than those in nerve or fibre, but higher utilization rate for plant. Therefore, this study implies the significance of keeping element dynamic balance in the alpine tundra ecosystem of Changbai Mountains.

Biomass↗

[Levels of toxic elements--Cd, Pb, Hg, Cr, Cu, Zn--in the blood and placenta of cows during parturition and in newborn calves].

It was demonstrated that mother's blood and the blood of new-born calves were contaminated by toxic elements in exposed and non-exposed area. The average Cd and Zn levels differed at high statistical significance (P less than 0.01) in the mothers blood from non-exposed regions in comparison with the average Cd and Zn levels from exposed region. The average residues of toxic elements in breeding cows placenta from the exposed and non-exposed regions were not statistically different. The average Zn content in new-born calves from non-exposed regions differ highly statistically significantly in comparison with the average Zn content in the blood of new-born calves from heifers of the exposed region. The transplacental ratio (TPx) of a toxic element in cow placenta during parturition was expressed from the average ratio of toxic element content in mother's blood: toxic element content in placenta: the toxic element content in blood of newborn calf, while the content of toxic element in mother's blood during parturition was expressed by a value equal to one. TPx in parturition period was expressed by mathematical formula TPx = 1 : Xp : Xk, where Xp = toxic element content in placenta, Xk = content of the toxic element in blood of new-born calf. TPPb, Hg, Cr, Cu, Zn values were not statistically different between the groups of breeding cows from exposed and non-exposed regions. TPCd in the group comprising 14 first-calves from the exposed region (TPCd = 1:0.89:2.59 in comparison with TPCd of six cows from non-exposed region, where TPCd = 1:0.29: 0.70;, differed statistically highly significantly (P less than .01). High statistical differences (P, less than 01) TPCd between these groups were explicitly affected highly statistically significantly (P less than .01) by different average Cd content in the blood of fourteen first-calves, compared with the average Cd content in blood of six cows from non-exposed region, in which the Cd value in blood during parturition was higher by 10(-1).

Animals↗

Transcriptional regulation of the rat glutathione S-transferase Ya subunit gene. Characterization of a xenobiotic-responsive element controlling inducible expression by phenolic antioxidants.

We have identified previously a xenobiotic-responsive element, which we termed the beta-naphthoflavone-responsive element, between nucleotide -722 and -682 in the 5'-flanking region of the rat glutathione S-transferase Ya subunit gene (Rushmore, T.H., King, R.G., Paulson, K.E., and Pickett, C.B. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 3826-3830). The beta-naphthoflavone-responsive element is responsible for part of the transcriptional activation of the Ya subunit gene by planar aromatic compounds but has a sequence distinct from the xenobiotic-responsive element found in multiple copies in the cytochrome P-450 IA1 gene and as a single copy in the Ya subunit gene. In the present study, we demonstrate that the beta-naphthoflavone-responsive element is required for the transcriptional activation of the Ya subunit gene by phenolic antioxidants such as t-butylhydroquinone through a mechanism that does not require functional Ah receptors. Furthermore, we present evidence that planar aromatic compounds must be metabolized before they transcriptionally activate the Ya subunit gene through the beta-naphthoflavone-responsive element. The transcriptional activation of the Ya subunit gene by planar aromatic compounds requires a functional Ah receptor. These data provide evidence that transcriptional activation of the glutathione S-transferase Ya subunit gene can be mediated by a novel xenobiotic-responsive element which is directly responsive to phenolic antioxidants such as t-butylhydroquinone. Hence we have named this new xenobiotic-responsive element the antioxidant-responsive element or ARE.

Animals↗

A retrovirus-like element occurs between the 3' breakpoints of two large deletions in the human beta-globin gene cluster.

We have identified a novel repetitive family in human DNA. One member of this family is found downstream of the beta-globin gene cluster between the 3' breakpoints of the deletions associated with Chinese G gamma + (A gamma delta beta)O thalassemia and HPFH-2. This repetitive element is approximately 6 kbp in length and includes terminal direct repeats of 415 bp. Numerous DNA sequence features of the direct repeats (LTRs) and their flanking regions indicate that the element is a retrovirus-like structure. The most striking of these features is the presence of a histidine tRNA binding site just 3' to the 5' LTR. Accordingly the element is named RTVL-H (retrovirus-like element-histidine). The LTRs of the RTVL-H element are not strongly homologous to the LTRs of any previously described mammalian retrovirus or retrovirus-like element. Copy number estimates suggest that there are approximately 1000 RTVL-H elements in the human genome. The element found 3' (greater than 60 kbp) to the beta-globin gene appears to be a stable part of the normal genome. This retrovirus-like element is brought close to the fetal gamma-globin locus by the Chinese thalassemia deletion but is deleted in HPFH-1 and HPFH-2.

Binding Sites↗

The rat vault RNA gene contains a unique RNA polymerase III promoter composed of both external and internal elements that function synergistically.

A novel gene transcribed by RNA polymerase (pol) III has been recently identified that produces an RNA component of a large cytoplasmic ribonucleoprotein complex (Kickhoefer, V. A., Searles, R. P., Kedersha, N. L., Garber, M. E., Johnson, D. L., and Rome, L. H. (1993) J. Biol. Chem. 268, 7868-7873). Since sequence analysis revealed that this gene contains promoter elements from two different classes of RNA pol III gene promoters, we examined the function of the 5'-flanking type-3 and internal type-2 sequences on transcription activity and the production of stable transcription complexes. We find that the vRNA gene contains a novel RNA pol III promoter, where both the external and internal sequences are essential for template activity and for the productive interaction of TFIIIC with the internal elements. Thus, the vRNA gene represents the first example of a template that requires both type-2 and type-3 promoter elements that appear to function synergistically in the formation of productive transcription complexes. We have further examined the function of the unique arrangement of an internal A box and two B box elements. We find that at least one B element is required for template activity. In the absence of the 5'-flanking sequence the presence of both B elements inhibits transcription and the binding of TFIIIC. The formation of active complexes is restored when either the B2 element is inactivated or the distance separating the two B elements is increased. Therefore, the B2 element appears to negatively regulate template activity in the absence of the upstream sequences. This unique RNA pol III promoter arrangement may provide a novel mechanism for the regulation of vRNA gene activity.

Animals↗

The upstream repression sequence from the yeast enolase gene ENO1 is a complex regulatory element that binds multiple trans-acting factors including REB1.

Cis-acting sequences that modulate ENO1 URS (upstream repression site) element activity were identified by base pair substitution mutagenesis. Base substitution mutations within three distinct regions of the 125-base pair URS element caused partial loss of URS activity in vivo. A URS element containing all three mutations was inactive. A binding site for the yeast REB1 protein was identified near the 5' terminus of the ENO1 URS element. Base substitution mutations that disrupted REB1 binding in vitro caused a 30% loss of URS activity in vivo. A second DNA binding activity was identified which also bound near the 5' terminus of the URS element. This latter binding activity was not antigenically related to REB1 nor was binding of this activity affected by base substitution mutations that abolished REB1 binding. Base substitution mutations within a second region of the ENO1 URS element caused a 38% loss of URS activity in vivo. The nucleotide sequence of this latter region is very similar to essential sequences within the URS elements from the yeast CAR1 and SSA1 genes, respectively. Base substitution mutations within a third region near the 3' terminus of the ENO1 URS element caused a 70% loss of URS activity in vivo. These latter sequences bound a partially purified factor that was distinct from REB1. These results showed that ENO1 URS element activity was modulated by multiple cis-acting sequences that bound distinct trans-acting factors.

Base Sequence↗

Identification of a novel repressive element that contributes to neuron-specific gene expression.

Multiple signaling pathways are thought to control the selective expression of genes over the course of neuronal differentiation. One approach to elucidating these pathways is to identify specific cis-acting elements that serve as the final targets for these signaling pathways in neural-specific genes. We now identify a novel repressive element from the growth-associated protein 43 (GAP-43) gene that can contribute to neuron-specific gene expression by inhibiting transcription in a wide range of non-neuronal cell types. This repressive element is located downstream of the GAP-43 TATA box and is highly position-dependent. When transferred to viral promoters this element preferentially inhibits transcription in non-neuronal cells. Electrophoretic mobility shift assays show that the repressive element comprises at least two protein recognition sites. One of these is a novel sequence motif that we designate the SNOG element, because it occurs downstream of the TATA boxes of the synaptosomal-associated protein of 25 kDa and neuronal nitric oxide synthase genes, as well as the GAP-43 gene. The GAP-43 repressive element is distinct in sequence and position dependence from the repressor element 1/neuron-restrictive silencer element previously described in other neural genes and therefore is a likely target for a distinct set of signaling pathways involved in the control of neuronal differentiation.

Animals↗

Characterization of the responsive elements to hormones in the rat aldolase B gene.

Transcription of the aldolase B gene, AldB, in the liver is regulated by hormones such as insulin and glucagon. To characterize the elements that are responsive to these hormones in the upstream region of AldB, plasmids carrying various length of the upstream region of this gene were constructed and transfected to primary cultured rat hepatocytes. The promoter activities were gradually increased by progressive deletion of the 5'-upstream region, and high activities were observed for constructs carrying the sequence between -408 and -85 bp, suggesting the presence of suppressive element(s) in the upstream region of -409 bp. The transcription activities of the mutants containing the sequences between -228 and -85 bp were enhanced by insulin, and glucagon suppressed the transcription activities of those containing the sequence between -764 and -85 bp. Two sequence elements similar to the cAMP-responsive element (CRE), one from -89 to -82 bp and another from +13 to +20 bp, were found in the upstream sequence of the gene. The latter element is not functional because its deletion did not affect either the transcription efficiency or glucagon response. However, the deletion of the former element diminished both functions. A gel retardation assay showed that the nuclear factor binds to the former element, which was competitive with authentic CRE oligonucleotide but not with the mutant CRE one. These results suggest that the CRE-like element in the promoter region is prerequisite for both fundamental transcription efficiency of the gene and suppression by glucagon in hepatocytes.

5' Untranslated Regions↗

A computerized induction analysis of possible co-variations among different elements in human tooth enamel.

In recent decades software tools in the area of artificial intelligence have rapidly developed for use in personal computers. Interactive rule induction utilizing mathematical algorithms has become a powerful tool in data analysis and in making rules and patterns explicit. Data from a Secondary Ion Mass Spectrometry (SIMS) elemental analysis of human dental enamel were used to elucidate co-variations between certain elements. A co-variation analysis was performed employing a computerized induction analysis program, as well as a neural network program. Both analyses, confirming each other, revealed co-variations between certain elements in dental enamel in addition to exclusion of data of no importance for chosen outcomes. The results are presented in hierarchic diagrams, in which the importance for every specific element is given by its position and level in the diagram (decision tree). From the results it became evident that elements such as chlorine and sodium expressed a high co-variation level. Similarly fluorine and potassium co-varied, as well as magnesium and the trace element strontium. It was demonstrated that data from an elemental analysis could be processed by an induction analysis to reveal co-variations between certain elements in tooth enamel. The biological significance of these data is not fully understood, and further analyses in the field are needed.

Algorithms↗

An Alu element from the K18 gene confers position-independent expression in transgenic mice.

We have identified a 323-base pair fragment of the 5'-flanking sequence of the K18 gene, which confers position-independent and copy number-dependent expression on two heterologous transgenes. This fragment is composed primarily of an Alu repetitive element. Its activity in mice is correlated with its RNA polymerase III promoter activity and its orientation-dependent ability to inhibit potential transcriptional interference in a transfection assay. However, the activity of the Alu element is not correlated with its enhancer blocking activity, a characteristic of insulator elements. In addition, this Alu element did not block the suppressive effect of co-injecting mouse alpha satellite DNA with the transgene. This Alu element is likely responsible for at least part of the protective effects of the sequences flanking the K18. These results suggest that transcriptionally active Alu elements may eliminate transcriptional interference of neighboring genes. This Alu element is one component of the locus control region associated with the K18 gene. Other Alu repetitive elements may also function to define regulatory domains.

Alkaline Phosphatase↗

Human follicle-stimulating hormone receptor (FSH-R) promoter/enhancer activity is inhibited by transcriptional factors, from the upstream stimulating factors family, via E-box and newly identified initiator element (Inr) in FSH-R non-expressing cells.

To localize the regulatory elements in the human follicle-stimulating hormone receptor (FSH-R) promoter/enhancer and to determine the role of upstream stimulatingfactors (USFs) in these elements, we transiently transfected constructs of FSH-R promoter/enhancer in pGL3 luciferase reporter plasmids into Chinese hamster ovary cells and the activities were determined by measuring luciferase luminescence of the cell lysates. The 5'-flanking regions of the human FSH-R gene from nt -1485 to -1 with respect to the gene translation start site were amplified by polymerase chain reaction (PCR) and subcloned in pGL3. Deletion mutants were created using PCR or restriction enzyme digestion. Mutation in the E-box sequence from nt -124 to -119 (E-box 3), in the construct from -224 to nt -1 or in the Inr element, which encompasses the transcriptional start site at nt -99, resulted in a substantial reduction in the human FSH-R promoter/enhancer activity. Overexpression of upstream stimulating factor-1 (USF1) suppresses the activity of the human FSH-R promoter/enhancer via Inr and E-box elements. Upstream stimulating factor-2 (USF2) decreases FSH-R promoter/enhancer activity by acting on E-box 3. The results indicate that E-box 3 and the Inr element are important elements of the human FSH-R promoter/ enhancer. USF family members inhibit FSH-R gene activity by acting via these elements. USF1 and USF2 suppress human FSH-R promoter/enhancer activity by acting on E-box 3. USF1 also decreases activity by interacting with the Inr element.

Animals↗

Tandem insertions of Alu elements.

Alu elements are non-autonomous, non-LTR retroposons that represent the most abundant mobile elements in the human genome (1.1 x 10(6) copies/genome). They preferentially insert adjacent to existing Alu elements. It has been proposed that Alu elements utilize LINE-1 machinery for their retroposition. The LINE-1 endonuclease cleaves at a loose consensus sequence. We have utilized a bioinformatics approach to show the order of insertion of pairs of young (Y) and old (S or J) Alu subfamily members. Our data suggest that the consensus LINE-1 endonuclease cleavage site used for insertion of the old Alu elements can be reused for integration of the younger ones inserting adjacent to them. However, there is also a preference at the 3' end of Alu into a non-ideal cleavage site that may represent unique properties of the A-tail for integration. Alu elements inserting adjacent to one another may suggest the saturation of the optimal integration sites with existing Alu elements, rather than any innate preference for Alu elements to integrate adjacent to other Alus.

Alu Elements↗