SEARCH · PubMed Health

Results for “Enhancer Elements, Genetic”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources

PubMed1986

Genome organization and nucleotide sequence of human papillomavirus type 33, which is associated with cervical cancer.

The 7,909-nucleotide sequence of human papillomavirus type 33, which is associated with cervical cancer, has been determined and used to deduce the corresponding genome arrangement. Extensive sequence homologies and other genetic features are shared with the related oncogenic virus, human papillomavirus type 16, especially in the major reading frames. A surprising difference was found in the noncoding region of human papillomavirus type 33 as, unlike all other sequenced papillomaviruses, it contains a perfect 78-base pair tandem repeat.

Base Sequence↗

PubMed1993

A novel hepatitis B virus (HBV) genetic element with Rev response element-like properties that is essential for expression of HBV gene products.

Many viruses possess complex mechanisms involving multiple gene products and cis-regulatory elements in order to achieve a fine control of their gene expression at both transcriptional and posttranscriptional levels. Hepatitis B virus (HBV) and retroviruses share many structural and functional similarities. In this study, by genetic and biochemical analyses, we have demonstrated the existence of a novel genetic element within the HBV genome which is essential for high-level expression of viral gene products. This element is located 3' to the envelope coding region. We have shown that this genetic element is cis acting at the posttranscriptional level and that its function is exerted at the level of RNA processing as part of transcribed sequences. This RNA element is also functional in the context of a heterologous gene. Similar to the function of Rev-Rev response element interaction of human immunodeficiency virus type 1, this element appears to inhibit the splicing process and facilitate the transport and utilization of HBV transcripts.

Base Sequence↗

PubMed1995

Differentially regulated expression of human IgG Fc receptor class III genes.

The expression of the human Fc receptor with low affinity for IgG (Fc gamma RIII, CD16) encoded by the Fc gamma RIII-A or Fc gamma RIII-B genes is restricted to natural killer (NK), a subset of T cells and macrophages or neutrophils (PMN). The genetic heterogeneity of Fc gamma RIII generates alternative membrane-anchored proteins with distinct signaling capacities when cross-linked by immune complexes. Of great importance is the characterization of the regulatory gene elements directing the expression of a particular Fc gamma RIII isoform to a given specific cell type. Molecular characterization of the Fc gamma RIII-A and Fc gamma RIII-B genes has revealed that the promoter regions display distinct tissue-specific transcriptional activities. In addition, the differential Fc gamma RIII-A/B gene activation can be regulated by enhancer elements located in the more upstream and intron regions. Transcription initiation in NK cells occurs also outside the normal promoter region by a second independent Fc gamma RIII-A promoter. Analysis of the additional Fc gamma RIIIa2-4 transcripts suggests the expression of novel, as yet unknown Fc gamma RIII receptor isoforms on NK cells.

Base Sequence↗

PubMed1998

A genetic screen to identify components of the sina signaling pathway in Drosophila eye development.

Specification of the R7 photoreceptor cell in the developing Drosophila eye requires the seven in absentia (sina) gene. We demonstrate that ectopic expression of sina in all cells behind the morphogenetic furrow disrupts normal eye development during pupation, resulting in a severely disorganized adult eye. Earlier events of cell fate specification appear unaffected. A genetic screen for dominant enhancers and suppressors of this phenotype identified mutations in a number of genes required for normal eye development, including UbcD1, which encodes a ubiquitin conjugating enzyme; SR3-4a, a gene previously implicated in signaling downstream of Ras1; and a Drosophila homolog of the Sin3A transcriptional repressor.

Amino Acid Sequence↗

PubMed2005

The origin of subfunctions and modular gene regulation.

Evolutionary explanations for the origin of modularity in genetic and developmental pathways generally assume that modularity confers a selective advantage. However, our results suggest that even in the absence of any direct selective advantage, genotypic modularity may increase through the formation of new subfunctions under near-neutral processes. Two subfunctions may be formed from a single ancestral subfunction by the process of fission. Subfunction fission occurs when multiple functions under unified genetic control become subdivided into more restricted functions under independent genetic control. Provided that population size is sufficiently small, random genetic drift and mutation can conspire to produce changes in the number of subfunctions in the genome of a species without necessarily altering the phenotype. Extensive genotypic modularity may then accrue in a near-neutral fashion in permissive population-genetic environments, potentially opening novel pathways to morphological evolution. Many aspects of gene complexity in multicellular eukaryotes may have arisen passively as population size reductions accompanied increases in organism size, with the adaptive exploitation of such complexity occurring secondarily.

Biological Evolution↗

PubMed1991

Identification of a transactivating function mapping to the putative immediate-early locus of human herpesvirus 6.

Sequencing studies have indicated that the unique component of the human herpesvirus 6 (HHV-6) genome and the unique long segment of the human cytomegalovirus genome are genetically colinear. Of particular interest is the identification of a region of local CpG dinucleotide suppression in the genome of HHV-6, a feature conserved in the genomes of human cytomegalovirus, murine cytomegalovirus, and simian cytomegalovirus, and a characteristic of the major immediate-early loci of these viruses. Adjacent to this region in HHV-6 are approximately 30 copies of a 103- to 108-bp sequence element, which contains consensus binding sites for the transcription factors AP2 and NF kappa B, in addition to a single KpnI recognition site. Together, these KpnI repeat units may compose an immediate-early enhancer, analogous to those found in the cytomegaloviruses. We present the sequence of this region of HHV-6 and demonstrate that a transactivating function is encoded by this region. We have used polymerase chain reaction to synthesize fragments containing open reading frames and 5' sequences with or without the upstream KpnI repeat units. Effector plasmids containing these HHV-6 coding and 5' sequences were able to effect activation of heterologous promoter-chloramphenicol acetyltransferase (CAT) constructs, including adenovirus E3-CAT and E4-CAT, human T-cell lymphotropic virus type I long terminal repeat (LTR)-CAT, and human immunodeficiency virus LTR-CAT, in cotransfection experiments in Vero cells and peripheral blood lymphocytes. Furthermore, we have identified the major open reading frame (RF4; 2.3 kb) as being essential for activation, and we have shown that the NF kappa B, SP1, and TATA box motifs in the human immunodeficiency virus LTR are all required for full induction of the promoter by the HHV-6-encoded transactivator.

Amino Acid Sequence↗

PubMed1997

Only a subset of the binary cell fate decisions mediated by Numb/Notch signaling in Drosophila sensory organ lineage requires Suppressor of Hairless.

In Drosophila, an adult external sensory organ (bristle) consists of four distinct cells which arise from a sensory organ precursor cell via two rounds of asymmetric divisions. The sensory organ precursor cell first divides to generate two secondary precursor cells, IIa and IIb. The IIa cell then divides to produce the hair cell and the socket cell. Shortly after, the IIb cell divides to generate the neuron and the sheath cell. The membrane-associated protein Numb has been shown to be required for the first two asymmetric divisions. We now report that a new hypomorphic numb mutant not only displays a double-socket phenotype, due to a hair cell to socket cell transformation, but also a double-sheath phenotype, due to a neuron to sheath cell transformation. This provides direct evidence that numb functions in the neuron/sheath cell lineage as well. Those results, together with our observation from immunofluorescence analysis that Numb forms a crescent in the dividing IIa and IIb cells suggest that asymmetric localization of Numb is important for the cell fate determination in all three asymmetric cell divisions in the sensory organ lineage. Interestingly, we found that in the hair/socket cell lineage but not the neuron/sheath cell lineage, a Suppressor of Hairless mutation acts as a dominant suppressor of numb mutations whereas Hairless mutations act as enhancers of numb. Moreover, epistasis analysis indicates that Suppressor of Hairless acts downstream of numb, and results from in vitro binding analysis suggest that the genetic interaction between numb and Hairless may occur through direct protein-protein interaction. These studies reveal that Suppressor of Hairless is required for only a subset of the asymmetric divisions that depend on the function of numb and Notch.

Animals↗

PubMed2001

Combinatorial transcriptional regulation: the interaction of transcription factors and cell signaling molecules with homeodomain proteins in Drosophila development.

Patterning and cell fate specification during development require complex interplay among multiple families of transcription factors to establish, maintain, and coordinate transcriptional cascades. During these processes, homeodomain proteins and cell signaling proteins cooperate to generate tissue-and stage-specific responses. This review of physical and genetic interactions in Drosophila melanogaster development highlights the cross-talk among these protein families. Protein-protein association can modulate regulation by both signal transduction-regulated transcription factors and homeodomain proteins, as observed in Drosophila and other organisms. Enhancers or genes regulated by multiple transcription factors provide opportunities for protein-protein binding to modulate transcription factor function. Combinatorial regulation of several enhancers by homeodomain proteins and cell signaling-regulated transcription factors is discussed; detailed maps of the genetic interactions that pattern the embryonic midgut and the larval wing imaginal disc are used to illustrate the multiplicity of potential protein-protein interactions. These interactions potentially provide direct mechanisms for communication between transcription factors as well as for generating the requisite functional specificity.

Animals↗

PubMed2002

Molecular characterization and developmental expression of the TFIIH factor p62 gene from Drosophila melanogaster: effects on the UV light sensitivity of a p62 mutant fly.

TFIIH is a multiprotein complex that has a central role in the RNA pol II mediated transcription, in DNA repair and in the control of the cell cycle. Mutations in some components of TFIIH are associated with three hereditary human syndromes: xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD). The p62 protein is a structural component of the TFIIH core and no syndromes have been identified up to date by mutations in this human gene. In this work we report the molecular and genetic characterization of the Drosophila melanogaster p62 gene (Dmp62). The Dmp62 gene product shows high identity with its human and mouse homologues. Using computer analysis we identified several common motifs in the p62 proteins from different organisms, suggesting that these motifs could be involved in possible protein-protein interactions within the TFIIH complex or with other transcription and DNA repair factors. The Dmp62 transcript is expressed at similar levels throughout development, although there is a significant increase of the transcript level during the late embryogenesis and in the adult male. The analysis of a Drosophila line with a P-element enhancer trap insertion at the Dmp62 5'-UTR that directs the lac-Z expression from the Dmp62 promoter, showed a high level of expression in the gut, the testis and the pericardial cells. A P-element that disrupts the Dmp62 gene (Dmp62mut) produces early embryo lethality in homozygous flies. Heterozygous Dmp62mut larvae are more sensitive to UV light irradiation, and those individuals that are able to develop into adults have severe abdominal cuticular damage after UV light irradiation.

Amino Acid Sequence↗

PubMed1998

Regulation of MHC class I and II gene transcription: differences and similarities.

Major histocompatibility complex (MHC) molecules serve as peptide receptors. These peptides are derived from processed cellular or extra-cellular antigens. The MHC gene complex encodes two major classes of molecules, MHC class I and class II, whose function is to present peptides to CD8+ (cytotoxic) and CD4+ (helper) T cells, respectively. The genes encoding both classes of MHC molecules seem to originate from a common ancestral gene. One of the hallmarks of the MHC is its extensive polymorphism which displays locus and allele-specific characteristics among the various MHC class I and class II genes. Because of its central role in immunosurveillance and in various disease states, the MHC is one of the best studied genetic systems. This review addresses several aspects of MHC class I and class II gene regulation in human and in particular, the contribution to the constitutive and cytokine-induced expression of MHC class I and II genes of MHC class-specific regulatory elements and regulatory elements which apparently are shared by the promoters of MHC class I and class II genes.

Animals↗

PubMed1989

Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence.

A DNA binding and dimerization motif, with apparent amphipathic helices (the HLH motif), has recently been identified in various proteins, including two that bind to immunoglobulin enhancers (E12 and E47). We show here that various HLH proteins can bind as apparent heterodimers to a single DNA motif and also, albeit usually more weakly, as apparent homodimers. The HLH domain can mediate heterodimer formation between either daughterless, E12, or E47 (Class A) and achaete-scute T3 or MyoD (Class B) to form proteins with high affinity for the kappa E2 site in the immunoglobulin kappa chain enhancer. The achaete-scute T3 and MyoD proteins do not form kappa E2-binding heterodimers together, and no active complex with N-myc was evident. The formation of a heterodimer between the daughterless and achaete-scute T3 products may explain the similar phenotypes of mutants at these two loci and the genetic interactions between them. A role of E12 and E47 in mammalian development, analogous to that of daughterless in Drosophila, is likely.

Animals↗

PubMed1997

Regulation of Drosophila spalt gene expression.

The region-specific homeotic gene spalt is involved in the specification of terminal versus trunk structures during early Drosophila embryogenesis. Later in development spalt activity participates in specific processes during organogenesis and larval imaginal disc development. The multiple functions of spalt are reflected in distinct spatio-temporal expression patterns throughout development. Here we show that spalt cis-regulatory sequences for region-specific and organ-specific expression are clustered. Their organization may provide the structural basis for the diversification of expression pattern within the spalt/spalt related/spalt adjacent gene complex. We also examined the transacting factor requirement for the blastodermal spalt expression domains. They are under the genetic control of maternal and gap gene products and we show that these products are able to bind to corresponding spalt cis-acting sequences in vitro. The results suggest that the transacting factors, as defined by genetic studies, functionally interact with the spalt regulatory region. In addition, we provide evidence that a zygotic gene product of the terminal system, Tailless, cooperates with the maternal gene product Caudal and thereby activates gene expression in the terminal region of the embryo.

Animals↗

PubMed1987

Sequence and centromere proximal location of a transformation enhancing fragment ans1 from Aspergillus nidulans.

The Aspergillus nidulans sequence ans1, previously known to enhance transformation frequencies of pyr4-based vectors, was shown to enhance the efficiency of argB and trpC-based vectors. Increased efficiencies could be obtained by constructing vectors containing argB and ans1 or by cotransforming selectable plasmids (containing argB, trpC, or pyr4) with the non-selectable ans1 sequence. The preponderance of evidence suggests that the mechanism of ans1 activity does not involve homologous recombination events, in spite of the presence of multiple regions of homology in the A. nidulans genome. Genetic mapping localized ans1 to the vicinity of the centromere of linkage group I. The nucleotide sequence of a 1.8 Kb functional subclone of ans1 was determined and found to be highly A + T rich (81%).

Aspergillus nidulans↗

PubMed2002

Cell fates and fusion in the C. elegans vulval primordium are regulated by the EGL-18 and ELT-6 GATA factors -- apparent direct targets of the LIN-39 Hox protein.

Development of the vulva in C. elegans is mediated by the combinatorial action of several convergent regulatory inputs, three of which, the Ras, Wnt and Rb-related pathways, act by regulating expression of the lin-39 Hox gene. LIN-39 specifies cell fates and regulates cell fusion in the mid-body region, leading to formation of the vulva. In the lateral seam epidermis, differentiation and cell fusion have been shown to be regulated by two GATA-type transcription factors, ELT-5 and -6. We report that ELT-5 is encoded by the egl-18 gene, which was previously shown to promote formation of a functional vulva. Furthermore, we find that EGL-18 (ELT-5), and its paralogue ELT-6, are redundantly required to regulate cell fates and fusion in the vulval primordium and are essential to form a vulva. Elimination of egl-18 and elt-6 activity results in arrest by the first larval stage; however, in animals rescued for this larval lethality by expression of ELT-6 in non-vulval cells, the post-embryonic cells (P3.p-P8.p) that normally become vulval precursor cells often fuse with the surrounding epidermal syncytium or undergo fewer than normal cell divisions, reminiscent of lin-39 mutants. Moreover, egl-18/elt-6 reporter gene expression in the developing vulva is attenuated in lin-39(rf) mutants, and overexpression of egl-18 can partially rescue the vulval defects caused by reduced lin-39 activity. LIN-39/CEH-20 heterodimers bind two consensus HOX/PBC sites in a vulval enhancer region of egl-18/elt-6, one of which is essential for vulval expression of egl-18/elt-6 reporter constructs. These findings demonstrate that the EGL-18 and ELT-6 GATA factors are essential, genetically redundant regulators of cell fates and fusion in the developing vulva and are apparent direct transcriptional targets of the LIN-39 Hox protein.

Animals↗

PubMed1993

Shigella flexneri invasion of HeLa cells induces NF-kappa B DNA-binding activity.

Although information about the genetic basis and mechanisms of Shigella flexneri cellular invasion is accumulating, little is known about changes in cell signaling and their consequences following bacterium-host cell interactions. A general result of signal transduction is alterations in the levels and/or activities of transcription factors. Alterations in transcription factor binding activities were observed following challenge with S. flexneri. Changes in the DNA-binding activities of cellular transcription factors to AP1, AP2, cyclic AMP response element, CTF1/NF1, NF-kappa B/Rel, OCT1, and SP1 DNA-binding sites were investigated by electrophoretic mobility shift assays. NF-kappa B/Rel DNA-binding activity was enhanced more than 11-fold by cellular invasion; noninvasive S. flexneri strains induced low levels of kappa B DNA binding. Both subunits of the NF-kappa B transcription factor, p50 and p65, but not c-Rel (p85), are components of the kappa B DNA-binding activity. These data suggest that changes in cellular transcription factor binding activity are a consequence of S. flexneri invasion, and these changes could play a role in the initial host response or in the pathogenesis of the disease.

Base Sequence↗

PubMed2005

Genomic sources of regulatory variation in cis and in trans.

Regulatory variation results from genetic changes with both cis and trans acting effects on gene expression. Here I describe the types of genetic variants that alter cis and trans regulation and discuss differences in the potential for cis and trans changes among different classes of genes. I argue that the molecular function of the protein encoded by each gene and how the gene is wired into the genomic regulatory network may influence its propensity for cis and trans regulatory changes.

Animals↗

PubMed2001

Mutations in Drosophila heat shock cognate 4 are enhancers of Polycomb.

The homeotic genes controlling segment identity in Drosophila are repressed by the Polycomb group of genes (PcG) and are activated by genes of the trithorax group (trxG). An F(1) screen for dominant enhancers of Polycomb yielded a point mutation in the heat shock cognate gene, hsc4, along with mutations corresponding to several known PcG loci. The new mutation is a more potent enhancer of Polycomb phenotypes than an apparent null allele of hsc4 is, although even the null allele occasionally displays homeotic phenotypes associated with the PcG. Previous biochemical results had suggested that HSC4 might interact with BRAHMA, a trxG member. Further analyses now show that there is no physical or genetic interaction between HSC4 and the Brahma complex. HSC4 might be needed for the proper folding of a component of the Polycomb repression complex, or it may be a functional member of that complex.

Alleles↗

PubMed2003

Duplication of U3 sequences in the long terminal repeat of mink cell focus-inducing viruses generates redundancies of transcription factor binding sites important for the induction of thymomas.

The ability of mink cell focus-inducing (MCF) viruses to induce thymomas is determined, in part, by transcriptional enhancers in the U3 region of their long terminal repeats (LTRs). To elucidate sequence motifs important for enhancer function in vivo, we injected newborn mice with MCF 1dr (supF), a weakly pathogenic, molecularly tagged (supF) MCF virus containing only one copy of a sequence that is present as two copies (known as the directly repeated [DR] sequence) in the U3 region of MCF 247 and analyzed LTRs from supF-tagged proviruses in two resulting thymomas. Tagged proviruses integrated upstream and in the reverse transcriptional orientation relative to c-myc provided the focus of our studies. These proviruses are thought to contribute to thymoma induction by enhancer-mediated deregulation of c-myc expression. The U3 region in a tagged LTR in one thymoma was cloned and sequenced. Relative to MCF 1dr (supF), the cloned U3 region contained an insertion of 140 bp derived predominantly from the DR sequence of the injected virus. The inserted sequence contains predicted binding sites for transcription factors known to regulate the U3 regions of various murine leukemia viruses. Similar constellations of binding sites were duplicated in two proviral LTRs integrated upstream from c-myc in a second thymoma. We replaced the U3 sequences in an infectious molecular clone of MCF 247 with the cloned proviral U3 sequences from the first thymoma and generated an infectious chimeric virus, MCF ProEn. When injected into neonatal AKR mice, MCF ProEn was more pathogenic than the parental virus, MCF 1dr (supF), as evidenced by the more rapid onset and higher incidence of thymomas. Molecular analyses of the resultant thymomas indicated that the U3 region of MCF ProEn was genetically stable. These data suggest that the arrangement and/or redundancy of transcription factor binding sites generated by specific U3 sequence duplications are important to the biological events mediated by MCF proviruses integrated near c-myc that contribute to transformation.

Animals↗