Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • PROMOTER  (19)
Collection
Keywords
  • 1
    Keywords: CANCER ; CELLS ; EXPRESSION ; INHIBITOR ; tumor ; BLOOD ; CELL ; DEATH ; GENE ; GENE-EXPRESSION ; GENES ; LINES ; DNA ; MECHANISM ; CELL-LINES ; ACID ; TRANSPORT ; CHROMATIN ; chromatin remodeling ; gene expression ; CELL-DEATH ; PROMOTER ; CELL-LINE ; leukemia ; LINE ; DNA methylation ; acetylation ; HISTONE DEACETYLASE ; histone deacetylase inhibitor ; METHYLATION ; HYPERMETHYLATION ; NORMAL CYTOGENETICS ; TUMOR-SUPPRESSOR ; METHYLTRANSFERASE ; REARRANGEMENT ; TRANSPORTER ; ADULT PATIENTS ; cell death ; SUPPRESSOR ; PROMOTER HYPERMETHYLATION ; USA ; DECITABINE ; H4 ; GROUP-B ; DNA-METHYLATION ; response ; tumor suppressor ; epigenetic ; ABERRANT METHYLATION ; PARTIAL TANDEM DUPLICATION ; ALL-1
    Abstract: Posttranslationally modified histones and DNA hypermethylation frequently interplay to deregulate gene expression in cancer. We report that acute myeloid leukemia (AML) with an aberrant histone methyltransferase, the mixed lineage leukemia partial tandem duplication (MLL-PTD), exhibits increased global DNA methylation versus AML with MLL-wildtype (MLL-WT-, P =.02). Among the differentially methylated genes, the SLC5A8 tumor suppressor gene (TSG) was more frequently hypermethylated (P =.003). In MLL-PTD+ cell lines having SLC5A8 promoter hypermethylation, incubation with decitabine activated SLC5A8 expression. Ectopic SLC5A8 expression enhanced histones H3 and H4 acetylation in response to the histone deacetylase inhibitor, valproate, consistent with the encoded protein-SMCT1-short-chain fatty acid transport function. In addition, enhanced cell death was observed in SMCT1-expressing MLL-PTD+ AML cells treated with valproate. Within the majority of MLL-PTD AML is a mechanism in which DNA hypermethylation silences a TSG that, together with MLL-PTD, can contribute further to aberrant chromatin remodeling and altered gene expression
    Type of Publication: Journal article published
    PubMed ID: 18566324
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; tumor ; CELL ; human ; MODEL ; DISEASE ; SITES ; GENE ; GENES ; transcription ; MICE ; NF-KAPPA-B ; COMPLEX ; COMPLEXES ; DNA ; MECHANISM ; murine ; TRANSCRIPTION FACTOR ; IMPACT ; animals ; mechanisms ; BINDING ; SEQUENCE ; SEQUENCES ; TARGET ; MOUSE ; STAGE ; TRANSCRIPTION FACTORS ; PROGRESSION ; MALIGNANCIES ; PATTERNS ; PROMOTER ; AGE ; transgenic ; leukemia ; DNA methylation ; TUMOR-SUPPRESSOR GENE ; REGION ; B-CELLS ; RECRUITMENT ; STRATEGIES ; MOUSE MODEL ; TARGETS ; REPRESSION ; METHYLATION ; TRANSCRIPTIONAL REPRESSION ; REGULATOR ; MALIGNANCY ; PROGRAM ; TUMOR-SUPPRESSOR ; CLL ; MURINE MODEL ; development ; BINDING-SITE ; USA ; EPIGENETICS ; ONSET ; CPG-ISLAND METHYLATION ; BINDING-SITES ; OCCURS ; tumor suppressor ; epigenetic ; STATE ; BINDING SITE ; histone modifications ; ABERRANT METHYLATION ; 3 ; therapeutic ; THERAPEUTIC TARGET ; WELL ; STRATEGY ; INVESTIGATE ; RATIONALE ; TRANSCRIPTION-FACTOR ; FOXD3
    Abstract: Epigenetic alterations, including gain or loss of DNA methylation, are a hallmark of nearly every malignancy. Changes in DNA methylation can impact expression of cancer-related genes including apoptosis regulators and tumor suppressors. Because such epigenetic changes are reversible, they are being aggressively investigated as potential therapeutic targets. Here we use the E mu-TCL1 transgenic mouse model of chronic lymphocytic leukemia (CLL) to determine the timing and patterns of aberrant DNA methylation, and to investigate the mechanisms that lead to aberrant DNA methylation. We show that CLL cells from E mu-TCL1 mice at various stages recapitulate epigenetic alterations seen in human CLL. Aberrant methylation of promoter sequences is observed as early as 3 months of age in these animals, well before disease onset. Abnormally methylated promoter regions include binding sites for the transcription factor FOXD3. We show that loss of Foxd3 expression due to an NF-kappa B p50/p50:HDAC1 repressor complex occurs in TCL1-positive B cells before methylation. Therefore, specific transcriptional repression is an early event leading to epigenetic silencing of target genes in murine and human CLL. These results provide strong rationale for the development of strategies to target NF-kappa B components in CLL and potentially other B-cell malignancies
    Type of Publication: Journal article published
    PubMed ID: 19666576
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: LUNG ; PROMOTER ; METHYLATION ; EXCISION-REPAIR ; 5-methylcytosine ; 5-HYDROXYMETHYLCYTOSINE ; MAMMALIAN DNA ; ACTIVE DNA DEMETHYLATION ; GLYCOSYLASE ; TET PROTEINS
    Abstract: DNA methylation is a dynamic and reversible process that governs gene expression during development and disease. Several examples of active DNA demethylation have been documented, involving genome-wide and gene-specific DNA demethylation. How demethylating enzymes are targeted to specific genomic loci remains largely unknown. We show that an antisense lncRNA, termed TARID (for TCF21 antisense RNA inducing demethylation), activates TCF21 expression by inducing promoter demethylation. TARID interacts with both the TCF21 promoter and GADD45A (growth arrest and DNA-damage-inducible, alpha), a regulator of DNA demethylation. GADD45A in turn recruits thymine-DNA glycosylase for base excision repair-mediated demethylation involving oxidation of 5-methylcytosine to 5-hydroxymethylcytosine in the TCF21 promoter by ten-eleven translocation methylcytosine dioxygenase proteins. The results reveal a function of lncRNAs, serving as a genomic address label for GADD45A-mediated demethylation of specific target genes.
    Type of Publication: Journal article published
    PubMed ID: 25087872
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: TYROSINE KINASE ; GENE-EXPRESSION ; TRANSGENIC MICE ; IDENTIFICATION ; PROMOTER ; leukemia ; PATHOGENESIS ; NPM-ALK ; HODGKIN LYMPHOMA ; MICRORNA-155
    Abstract: Anaplastic large cell lymphoma (ALCL) is a rare, aggressive, non-Hodgkin's lymphoma that is characterized by CD30 expression and disease onset in young patients. About half of ALCL patients bear the t(2;5)(p23;q35) translocation, which results in the formation of the nucleophosmin-anaplastic lymphoma tyrosine kinase (NPM-ALK) fusion protein (ALCL ALK(+) ). However, little is known about the molecular features and tumour drivers in ALK-negative ALCL (ALCL ALK(-) ), which is characterized by a worse prognosis. We found that ALCL ALK(-) , in contrast to ALCL ALK(+) , lymphomas display high miR-155 expression. Consistent with this, we observed an inverse correlation between miR-155 promoter methylation and miR-155 expression in ALCL. However, no direct effect of the ALK kinase on miR-155 levels was observed. Ago2 immunoprecipitation revealed miR-155 as the most abundant miRNA, and enrichment of target mRNAs C/EBPbeta and SOCS1. To investigate its function, we over-expressed miR-155 in ALCL ALK(+) cell lines and demonstrated reduced levels of C/EBPbeta and SOCS1. In murine engraftment models of ALCL ALK(-) , we showed that anti-miR-155 mimics are able to reduce tumour growth. This goes hand-in-hand with increased levels of cleaved caspase-3 and high SOCS1 in these tumours, which leads to suppression of STAT3 signalling. Moreover, miR-155 induces IL-22 expression and suppresses the C/EBPbeta target IL-8. These data suggest that miR-155 can act as a tumour driver in ALCL ALK(-) and blocking miR-155 could be therapeutically relevant. Original miRNA array data are to be found in the supplementary material (Table S1). Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    Type of Publication: Journal article published
    PubMed ID: 25820993
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: RECEPTOR ; EXPRESSION ; COMBINATION ; PHASE-I ; TOXICITY ; GENE ; transcription ; DRUG ; PATIENT ; COMPLEX ; RESPONSES ; COMPLEXES ; DNA ; ACID ; PROMOTER ; AGE ; FUSION ; leukemia ; DNA methylation ; DNA methyltransferase ; ESTROGEN-RECEPTOR ; ACUTE PROMYELOCYTIC LEUKEMIA ; HYPOMETHYLATION ; TRANS-RETINOIC ACID ; AGENT ; SINGLE ; ONCOLOGY ; RE ; END ; DEMETHYLATION ; METHYLTRANSFERASE ; ESTROGEN ; ENZYME ; analysis ; methods ; PHASE ; estrogen receptor ; USA ; MLL ; DEPLETION ; Phase I ; MYELODYSPLASTIC SYNDROMES ; 5-AZA-2'-DEOXYCYTIDINE ; POINT ; HISTONE DEACETYLASE INHIBITION ; in combination ; phase I study
    Abstract: Purpose To determine an optimal biologic dose ( OBD) of decitabine as a single agent and then the maximum- tolerated dose ( MTD) of valproic acid ( VA) combined with decitabine in acute myeloid leukemia ( AML). Patients and Methods Twenty-five patients ( median age, 70 years) were enrolled; 12 were untreated and 13 had relapsed AML. To determine an OBD ( based on a gene re-expression end point), 14 patients received decitabine alone for 10 days. To determine the MTD, 11 patients received decitabine ( at OBD, days 1 through 10) plus dose-escalating VA ( days 5 through 21). Results The OBD of decitabine was 20 mg/m(2)/d intravenously, with limited nonhematologic toxicity. In patients treated with decitabine plus VA, dose- limiting encephalopathy occurred in two of two patients at VA 25 mg/ kg/d and one of six patients at VA 20 mg/ kg/d. Drug- induced re- expression of estrogen receptor ( ER) was associated with clinical response ( P 〈=.05). ER promoter demethylation, global DNA hypomethylation, depletion of DNA methyltransferase enzyme, and histone hyperacetylation were also observed. In an intent-to-treat analysis, the response rate was 44% ( 11 of 25). Of 21 assessable patients, 11 ( 52%) responded: four with morphologic and cytogenetic complete remission ( CR; each had complex karyotype), four with incomplete CR, and three with partial remission. In untreated AML, four of nine assessable patients achieved CR. Clinical responses appeared similar for decitabine alone or with VA. Conclusion Low-dose decitabine was safe and showed encouraging clinical and biologic activity in AML, but the addition of VA led to encephalopathy at relatively low doses. On the basis of these results, additional studies of decitabine ( 20 mg/m(2)/d for 10 days) alone or with an alternative deacetylating agent are warranted
    Type of Publication: Journal article published
    PubMed ID: 17679729
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: CANCER ; EXPRESSION ; IN-VITRO ; tumor ; carcinoma ; CELL ; human ; IN-VIVO ; LUNG ; VITRO ; VIVO ; lung cancer ; LUNG-CANCER ; SITE ; GENE ; microarray ; PROTEIN ; SAMPLE ; SAMPLES ; transcription ; cell line ; DIFFERENTIATION ; LINES ; TIME ; DNA ; MECHANISM ; TRANSCRIPTION FACTOR ; MARKER ; prognosis ; mechanisms ; BINDING ; cell cycle ; CELL-CYCLE ; CELL-LINES ; CYCLE ; DOWN-REGULATION ; treatment ; ALPHA ; PROMOTER ; MUTATION ; CELL-LINE ; LINE ; DNA methylation ; HETEROZYGOSITY ; inactivation ; REGION ; US ; HEAD ; INVOLVEMENT ; NECK ; squamous cell carcinoma ; OVEREXPRESSION ; POOR-PROGNOSIS ; cell lines ; expression profiling ; METHYLATION ; CYCLE CONTROL ; C/EBP-ALPHA ; BINDING PROTEIN ; CELL CARCINOMA ; ONCOLOGY ; ENHANCER ; BINDING-PROTEIN ; RE ; TUMOR-SUPPRESSOR ; DEMETHYLATION ; HNSCC ; SUPPRESSOR ; USA ; LOSSES ; head and neck squamous cell carcinoma ; EPIGENETICS ; cancer research ; in vivo ; UPSTREAM REGULATORY REGION ; SQUAMOUS-CELL ; 5-AZA-2'-DEOXYCYTIDINE ; UPSTREAM ; DNA-METHYLATION ; cell cycle control ; INVOLUCRIN PROMOTER ACTIVITY
    Abstract: Tumor suppressor CCAAT enhancer binding protein a (C/EBP alpha) is a transcription factor involved in cell cycle control and cellular differentiation. In a recent study, microarray expression profiling on head and neck squamous cell carcinoma (HNSCC) samples identified significant C/EBP alpha down-regulation, correlating with poor prognosis. However, the mechanisms of C/EBP alpha down-regulation remained elusive. C/EBP alpha has been previously found to provide an antiproliferative role in lung cancer, and our laboratory showed that its down-regulation involves epigenetic mechanisms. This prompted us to investigate the involvement of epigenetics in down-regulating C/EBP alpha in HNSCC. Here, we show that C/EBP alpha is down-regulated in HNSCC by loss of heterozygosity and DNA methylation, but not by gene mutation. We found a consistently methylated upstream regulatory region (-1,399 bp to -1,253 bp in relation to the transcription start site) in 68% of the HNSCC tumor samples, and DNA demethylation using 5-aza-2'-deoxycytidine treatment was able to significantly restore C/EBP alpha mRNA expression in the HNSCC cell lines we tested. In addition, C/EBP alpha overexpression in a HNSCC cell line (SCC22B) revealed its ability to provide tumor suppressor activity in HNSCC in vitro and in vivo. In conclusion, we showed for the first time not only that C/EBP alpha has tumor suppressor activity in HNSCC, but also that it is down-regulated by DNA promoter methylation
    Type of Publication: Journal article published
    PubMed ID: 17510391
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: CANCER ; CELLS ; EXPRESSION ; BLOOD ; CELL ; human ; KINASE ; DISEASE ; PROTEIN ; FAMILY ; TRANSCRIPTION FACTOR ; BINDING ; BIOLOGY ; MEMBER ; MEMBERS ; MOLECULAR-BIOLOGY ; protein kinase ; PROTEIN-KINASE ; NO ; CELL-DEATH ; PROMOTER ; MUTATION ; leukemia ; Jun ; PHENOTYPE ; METHYLATION ; molecular biology ; molecular ; PROGRAM ; RE ; FAMILIES ; ALLELE ; chronic lymphocytic leukemia ; CLL ; heritability ; HAPLOTYPE ; EVENTS ; PREDISPOSITION ; USA ; LOSSES ; PROMOTER METHYLATION ; B-CELL ; KINASE-1 ; REDUCED EXPRESSION ; TUMOR-SUPPRESSOR GENES ; CpG island ; CHRONIC-LYMPHOCYTIC-LEUKEMIA ; OCCURS ; death associated protein kinase 1 ; APOPTOTIC CHECKPOINT ; DNA HYPERMETHYLATION ; P2X7 RECEPTOR GENE
    Abstract: The heritability of B cell chronic lymphocytic leukemia (CLL) is relatively high; however, no predisposing mutation has been convincingly identified. We show that loss or reduced expression of death-associated protein kinase 1 (DAPK1) underlies cases of heritable predisposition to CLL and the majority of sporadic CLL. Epigenetic silencing of DAPK1 by promoter methylation occurs in almost all sporadic CLL cases. Furthermore, we defined a disease haplotype, which segregates with the CLL phenotype in a large family. DAM expression of the CLL allele is downregulated by 75% in germline cells due to increased HOXB7 binding. In the blood cells from affected family members, promoter methylation results in additional loss of DAM expression. Thus, reduced expression of DAM can result from germline predisposition, as well as epigenetic or somatic events causing or contributing to the CILL phenotype
    Type of Publication: Journal article published
    PubMed ID: 17540169
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: CANCER ; EXPRESSION ; IN-VITRO ; CELL ; Germany ; VITRO ; SYSTEM ; GENE-EXPRESSION ; PROTEIN ; transcription ; DIFFERENTIATION ; PATIENT ; DNA ; MECHANISM ; TRANSCRIPTION FACTOR ; mechanisms ; BINDING ; CELL-LINES ; DOWN-REGULATION ; ALPHA ; TARGET ; PROMOTER ; CELL-LINE ; leukemia ; DNA methylation ; REGION ; PREDICTION ; TARGETS ; protein expression ; C/EBP-ALPHA ; BINDING PROTEIN ; ONCOLOGY ; RE ; LEVEL ; HUMAN CANCER-CELLS ; USA ; LOSSES ; PROMOTER REGION ; cancer research ; valproic acid ; SMALL RNAS ; UPSTREAM ; DNA-METHYLATION ; block ; modification ; UNTRANSLATED REGION ; epigenetic ; DOWN-MODULATION ; MICRORNA GENE
    Abstract: Functional loss of CCAAT/enhancer binding protein alpha (C/ EBP alpha), a master regulatory transcription factor in the hematopoietic system, can result in a differentiation block in granulopoiesis and thus contribute to leukemic transformation. Here, we show the effect of epigenetic aberrations in regulating C/EBP alpha expression in acute myeloid leukemia (AML). Comprehensive DNA methylation analyses of the CpG island of C/EBP alpha identified a densely methylated upstream promoter region in 51% of AML, patients. Aberrant DNA methylation was strongly associated with two generally prognostically favorable cytogenetic subgroups: inv(16) and t(15;17). Surprisingly, while epigenetic treatment increased C/EBP alpha mRNA levels in vitro, C/EBP alpha protein levels decreased. Using a computational microRNA (miRNA) prediction approach and functional studies, we show that C/EBP alpha mRNA is a target for miRNA-124a. This miRNA is frequently silenced by epigenetic mechanisms in leukemia cell lines, becomes up-regulated after epigenetic treatment, and targets the C/EBP alpha 3' untranslated region. In this way, C/EBP alpha protein expression is reduced in a posttranscriptional manner. Our results indicate that epigenetic alterations of C/EBP alpha are a frequent event in AML and that epigenetic treatment can result in down-regulation of a key hematopoietic transcription factor
    Type of Publication: Journal article published
    PubMed ID: 18451139
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: CELLS ; EXPRESSION ; CELL ; human ; NETWORKS ; SITE ; SITES ; DISTINCT ; GENE ; GENE-EXPRESSION ; GENES ; GENOME ; microarray ; RNA ; transcription ; LINES ; MECHANISM ; mechanisms ; IDENTIFICATION ; PATTERNS ; gene expression ; microarrays ; PROMOTER ; PROMOTERS ; genetics ; HUMAN GENOME ; HUMAN GENES ; METHYLATION ; heredity ; PATTERN ; GENOME-WIDE ANALYSIS ; ARRAY ; genomics ; RESOURCE ; analysis ; CHIP ; USA ; microbiology ; ENGLAND ; biotechnology ; PLATFORM ; BREAST-CANCER CELLS ; synthesis ; STATE ; GENOME-WIDE ; ESTROGEN-RECEPTOR-ALPHA ; TRANSCRIPTION INITIATION
    Abstract: Background: Independent lines of evidence suggested that a large fraction of human genes possess multiple promoters driving gene expression from distinct transcription start sites. Understanding which promoter is employed in which cellular context is required to unravel gene regulatory networks within the cell. Results: We have developed a custom microarray platform that tiles roughly 35,000 alternative putative promoters from nearly 7,000 genes in the human genome. To demonstrate the utility of this array platform, we have analyzed the patterns of promoter usage in 17 beta-estradiol (E2)-treated and untreated MCF7 cells and show widespread usage of alternative promoters. Most intriguingly, we show that the downstream promoter in E2-sensitive multiple promoter genes tends to be very close to the 3'-terminus of the gene, suggesting exotic mechanisms of expression regulation in these genes. Conclusion: The usage of alternative promoters greatly multiplies the transcriptional complexity available within the human genome. The fact that many of these promoters are incapable of driving the synthesis of a meaningful protein-encoding transcript further complicates the story
    Type of Publication: Journal article published
    PubMed ID: 18655706
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Keywords: CELLS ; EXPRESSION ; BLOOD ; CELL ; Germany ; SITES ; GENE ; PROTEIN ; RNA ; transcription ; ACCUMULATION ; PATIENT ; MECHANISM ; TRANSCRIPTION FACTOR ; BINDING ; SUPPRESSION ; DISORDER ; TARGET ; IDENTIFICATION ; DISRUPTION ; ASSAY ; PROMOTER ; PROMOTERS ; leukemia ; PATHOGENESIS ; REGION ; B-CELLS ; ONCOGENE ; PREDICTION ; REVEALS ; OVEREXPRESSION ; mutagenesis ; expression profiling ; METHYLATION ; protein expression ; TRANSLOCATIONS ; DISORDERS ; CLL ; regulation ; mRNA ; development ; LEVEL ; ASSAYS ; TECHNOLOGY ; RNAS ; BINDING-SITE ; USA ; BINDING-SITES ; B-CELL ; MicroRNAs ; miRNA ; hematology ; MICRORNA ; epigenetic ; BINDING SITE ; Luciferase reporter ; 3 ; TRANSCRIPTION-FACTOR ; HOST GENES ; MICRORNA TARGETS
    Abstract: MicroRNAs (miRNA) play a key role in cellular regulation and, if deregulated, in the development of neoplastic disorders including chronic lymphocytic leukemia (CLL). RNAs from primary cells of 50 treatment-naive CLL patients and peripheral B cells of 14 healthy donors were applied to miRNA expression profiling using bead chip technology. In CLL cells, a set of 7 up-and 19 down-regulated miRNAs was identified. Among the miRNAs down-regulated in CLL cells, 6 of 10 miRNA promoters examined showed gain of methylation compared with normal B-cell controls. Subsequent target prediction of deregulated miRNAs revealed a highly significant binding prediction at the 3' untranslated region of the pleomorphic adenoma gene 1 (PLAG1) oncogene. Luciferase reporter assays including site-directed mutagenesis of binding sites revealed a significant regulation of PLAG1 by miR-181a, miR-181b, miR-107, and miR-424. Although expression of PLAG1 mRNA was not affected, PLAG1 protein expression was shown to be significantly elevated in CLL cells compared with the levels in healthy donor B cells. In summary, we could demonstrate disruption of miRNA-mediated translational control, partly due to epigenetic transcriptional silencing of miRNAs, with subsequent overexpression of the oncogenic transcription factor PLAG1 as a putative novel mechanism of CLL pathogenesis. (Blood. 2009; 114: 3255-3264)
    Type of Publication: Journal article published
    PubMed ID: 19692702
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...