TY - JOUR A1 - Djakovic, Lara A1 - Hennig, Thomas A1 - Reinisch, Katharina A1 - Milić, Andrea A1 - Whisnant, Adam W. A1 - Wolf, Katharina A1 - Weiß, Elena A1 - Haas, Tobias A1 - Grothey, Arnhild A1 - Jürges, Christopher S. A1 - Kluge, Michael A1 - Wolf, Elmar A1 - Erhard, Florian A1 - Friedel, Caroline C. A1 - Dölken, Lars T1 - The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes JF - Nature Communications N2 - Herpes simplex virus 1 (HSV-1) infection and stress responses disrupt transcription termination by RNA Polymerase II (Pol II). In HSV-1 infection, but not upon salt or heat stress, this is accompanied by a dramatic increase in chromatin accessibility downstream of genes. Here, we show that the HSV-1 immediate-early protein ICP22 is both necessary and sufficient to induce downstream open chromatin regions (dOCRs) when transcription termination is disrupted by the viral ICP27 protein. This is accompanied by a marked ICP22-dependent loss of histones downstream of affected genes consistent with impaired histone repositioning in the wake of Pol II. Efficient knock-down of the ICP22-interacting histone chaperone FACT is not sufficient to induce dOCRs in ΔICP22 infection but increases dOCR induction in wild-type HSV-1 infection. Interestingly, this is accompanied by a marked increase in chromatin accessibility within gene bodies. We propose a model in which allosteric changes in Pol II composition downstream of genes and ICP22-mediated interference with FACT activity explain the differential impairment of histone repositioning downstream of genes in the wake of Pol II in HSV-1 infection. KW - herpes virus KW - transcription Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358161 VL - 14 ER - TY - THES A1 - Fetiva Mora, Maria Camila T1 - Changes in chromatin accessibility by oncogenic YAP and its relevance for regulation of cell cycle gene expression and cell migration T1 - Änderungen der Chromatinzugänglichkeit durch onkogene YAP und seine Relevanz für die Genexpression während des Zellzyklus und für die Zellmigration N2 - Various types of cancer involve aberrant cell cycle regulation. Among the pathways responsible for tumor growth, the YAP oncogene, a key downstream effector of the Hippo pathway, is responsible for oncogenic processes including cell proliferation, and metastasis by controlling the expression of cell cycle genes. In turn, the MMB multiprotein complex (which is formed when B-MYB binds to the MuvB core) is a master regulator of mitotic gene expression, which has also been associated with cancer. Previously, our laboratory identified a novel crosstalk between the MMB-complex and YAP. By binding to enhancers of MMB target genes and promoting B-MYB binding to promoters, YAP and MMB co-regulate a set of mitotic and cytokinetic target genes which promote cell proliferation. This doctoral thesis addresses the mechanisms of YAP and MMB mediated transcription, and it characterizes the role of YAP regulated enhancers in transcription of cell cycle genes. The results reported in this thesis indicate that expression of constitutively active, oncogenic YAP5SA leads to widespread changes in chromatin accessibility in untransformed human MCF10A cells. ATAC-seq identified that newly accessible and active regions include YAP-bound enhancers, while the MMB-bound promoters were found to be already accessible and remain open during YAP induction. By means of CRISPR-interference (CRISPRi) and chromatin immuniprecipitation (ChIP), we identified a role of YAP-bound enhancers in recruitment of CDK7 to MMB-regulated promoters and in RNA Pol II driven transcriptional initiation and elongation of G2/M genes. Moreover, by interfering with the YAP-B-MYB protein interaction, we can show that binding of YAP to B-MYB is also critical for the initiation of transcription at MMB-regulated genes. Unexpectedly, overexpression of YAP5SA also leads to less accessible chromatin regions or chromatin closing. Motif analysis revealed that the newly closed regions contain binding motifs for the p53 family of transcription factors. Interestingly, chromatin closing by YAP is linked to the reduced expression and loss of chromatin-binding of the p53 family member Np63. Furthermore, I demonstrate that downregulation of Np63 following expression of YAP is a key step in driving cellular migration. Together, the findings of this thesis provide insights into the role of YAP in the chromatin changes that contribute to the oncogenic activities of YAP. The overexpression of YAP5SA not only leads to the opening of chromatin at YAP-bound enhancers which together with the MMB complex stimulate the expression of G2/M genes, but also promotes the closing of chromatin at ∆Np63 -bound regions in order to lead to cell migration. N2 - Ein Kennzeichen vieler Tumoren ist die fehlerhafte Aktivierung von zellzyklusregulierenden Signalwegen. Ein für das Tumorwachstum wichtiger Signalwege ist der Hippo-Signalweg und das durch ihn regulierte Onkogen YAP, ein transkriptioneller Koaktivator. Durch die Regulierung von Zellzyklusgenen ist YAP verantwortlich für onkogene Prozesse wie Zellproliferation und Metastasierung. Der MMB-Multiproteinkomplex wiederum – er entsteht, wenn B-MYB an das MuvB-Kernmodul bindet – ist ein wichtiger Regulator der mitotischen Genexpression, welche ebenso mit der Tumorentstehung in Verbindung gebracht wurde. Unser Labor hat zuvor einen neuen Mechanismus der Regulation mitotischer Gene durch den MMB-Komplex und YAP identifiziert: Durch die Bindung an Enhancer der MMB-Zielgene und die Förderung der B-MYB-Bindung an Promotoren reguliert YAP eine Reihe von mitotischen und zytokinetischen Zielgenen, welche die Zellproliferation fördern. Diese Doktorarbeit befasst sich mit den Mechanismen der YAP- und MMB-vermittelten Transkription und charakterisiert die Rolle der YAP regulierten Enhancer während der Transkription von Zellzyklusgenen. Die in dieser Dissertation dargelegten Ergebnisse zeigen, dass die Expression von konstitutiv aktivem, onkogenem YAP5SA zu weitreichenden Veränderungen in der Chromatinzugänglichkeit nicht-transformierter humaner MCF10A Zellen führt. ATAC-seq zeigte, dass ein grosse Anzahl YAP-gebundene Enhancer zugänglich und aktiviert werden. Gleichzeitig konnte festgestellt werden, dass die MMB-gebundenen Promotoren bereits vor der Expression von YAP zugänglich sind und während der YAP-Induktion offen bleiben. Mittels CRISP-Interferenz (CRISPRi) und Chromatin-Immunpräzipitationen (ChIP) konnten wir zeigen, dass YAP-gebundene Enhancer die Rekrutierung von CDK7 an MMB-regulierten Promotoren sowie die Initiation und Elongation der Transkription von G2/M Genen fördert. Durch die experimentelle Blockade der YAP-B-MYB Proteininteraktion konnten wir darüber hinaus belegen, dass auch die Bindung von YAP an B-MYB für die Initiation der Transkription an MMB-regulierten Genen entscheidend ist. Unerwarteterweise führte die Überexpression von YAP5SA auch dazu, dass bestimmte Regionen im Genom weniger zugänglich werden. Motivanalysen ergaben, dass diese neu geschlossenen Regionen Bindungsmotive für die p53-Familie von Transkriptionsfaktoren enthalten. Die Chromatinschließung durch YAP ist an eine reduzierte Expression und an den Verlust der Chromatinbindung des p53-Familienmitglieds Np63 gekoppelt. Schließlich konnte gezeigt werden, dass die Inhibition von Np63 durch YAP ein wichtiger Schritt in der YAP-abhängigen Förderung der Zellmigration ist. Zusammenfassend liefern die Ergebnisse dieser Dissertation Einblicke in die Rolle von YAP bei Chromatinveränderungen welche zu den onkogenen Aktivitäten von YAP beitragen. Die Überexpression von YAP führt dabei einerseits zur Öffnung des Chromatins an YAP-gebundenen Enhancern, die zusammen mit dem MMB-Komplex die Expression von G2/M Genen stimulieren. Andererseits fördert YAP auch das Schließen von Chromatin an Np63-gebundenen Regionen, was wiederum Zellmigration nach sich zieht. KW - YAP KW - B-MYB KW - MMB KW - enhancers KW - transcription KW - chromatin accessibility KW - opening of chromatin KW - closing of chromatin KW - cell migration KW - G2/M genes KW - Chromatin KW - Genexpression KW - Zellzyklus KW - Zellmigration Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-302910 ER - TY - JOUR A1 - Pattschull, Grit A1 - Walz, Susanne A1 - Gründl, Marco A1 - Schwab, Melissa A1 - Rühl, Eva A1 - Baluapuri, Apoorva A1 - Cindric-Vranesic, Anita A1 - Kneitz, Susanne A1 - Wolf, Elmar A1 - Ade, Carsten P. A1 - Rosenwald, Andreas A1 - von Eyss, Björn A1 - Gaubatz, Stefan T1 - The Myb-MuvB complex is required for YAP-dependent transcription of mitotic genes JF - Cell Reports N2 - YAP and TAZ, downstream effectors of the Hippo pathway, are important regulators of proliferation. Here, we show that the ability of YAP to activate mitotic gene expression is dependent on the Myb-MuvB (MMB) complex, a master regulator of genes expressed in the G2/M phase of the cell cycle. By carrying out genome-wide expression and binding analyses, we found that YAP promotes binding of the MMB subunit B-MYB to the promoters of mitotic target genes. YAP binds to B-MYB and stimulates B-MYB chromatin association through distal enhancer elements that interact with MMB-regulated promoters through chromatin looping. The cooperation between YAP and B-MYB is critical for YAP-mediated entry into mitosis. Furthermore, the expression of genes coactivated by YAP and B-MYB is associated with poor survival of cancer patients. Our findings provide a molecular mechanism by which YAP and MMB regulate mitotic gene expression and suggest a link between two cancer-relevant signaling pathways. KW - YAP KW - B-MYB KW - Myb-MuvB KW - mitotic genes KW - enhancer KW - transcription Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202039 VL - 27 IS - 12 ER - TY - JOUR A1 - Elkon, Ran A1 - Loayza-Puch, Fabricio A1 - Korkmaz, Gozde A1 - Lopes, Rui A1 - van Breugel, Pieter C A1 - Bleijerveld, Onno B A1 - Altelaar, AF Maarten A1 - Wolf, Elmar A1 - Lorenzin, Francesca A1 - Eilers, Martin A1 - Agami, Reuven T1 - Myc coordinates transcription and translation to enhance transformation and suppress invasiveness JF - EMBO reports N2 - c‐Myc is one of the major human proto‐oncogenes and is often associated with tumor aggression and poor clinical outcome. Paradoxically, Myc was also reported as a suppressor of cell motility, invasiveness, and metastasis. Among the direct targets of Myc are many components of the protein synthesis machinery whose induction results in an overall increase in protein synthesis that empowers tumor cell growth. At present, it is largely unknown whether beyond the global enhancement of protein synthesis, Myc activation results in translation modulation of specific genes. Here, we measured Myc‐induced global changes in gene expression at the transcription, translation, and protein levels and uncovered extensive transcript‐specific regulation of protein translation. Particularly, we detected a broad coordination between regulation of transcription and translation upon modulation of Myc activity and showed the connection of these responses to mTOR signaling to enhance oncogenic transformation and to the TGFβ pathway to modulate cell migration and invasiveness. Our results elucidate novel facets of Myc‐induced cellular responses and provide a more comprehensive view of the consequences of its activation in cancer cells. KW - c‐Myc KW - transcriptional responses KW - translational regulation KW - transcription KW - transformation KW - metastasis KW - cancer KW - protein biosynthesis & quality control Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150373 VL - 16 IS - 12 ER - TY - JOUR A1 - Naseem, Muhammad A1 - Dandekar, Thomas T1 - The Role of Auxin-Cytokinin Antagonism in Plant-Pathogen Interactions JF - PLOS Pathogens N2 - No abstract available. KW - disease KW - pseudomas-syringae KW - arabidpsis thaliana KW - immunity KW - organogenesis KW - transcription KW - resistance KW - crosstalk Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131901 VL - 8 IS - 11 ER - TY - JOUR A1 - Gassen, Alwine A1 - Brechtefeld, Doris A1 - Schandry, Niklas A1 - Arteaga-Salas, J. Manuel A1 - Israel, Lars A1 - Imhof, Axel A1 - Janzen, Christian J. T1 - DOT1A-dependent H3K76 methylation is required for replication regulation in Trypanosoma brucei JF - Nucleic Acids Research N2 - Cell-cycle progression requires careful regulation to ensure accurate propagation of genetic material to the daughter cells. Although many cell-cycle regulators are evolutionarily conserved in the protozoan parasite Trypanosoma brucei, novel regulatory mechanisms seem to have evolved. Here, we analyse the function of the histone methyltransferase DOT1A during cell-cycle progression. Over-expression of DOT1A generates a population of cells with aneuploid nuclei as well as enucleated cells. Detailed analysis shows that DOT1A over-expression causes continuous replication of the nuclear DNA. In contrast, depletion of DOT1A by RNAi abolishes replication but does not prevent karyokinesis. As histone H3K76 methylation has never been associated with replication control in eukaryotes before, we have discovered a novel function of DOT1 enzymes, which might not be unique to trypanosomes. KW - variants KW - cell-cycle regulation KW - blood-stream forms KW - african trypanosomes KW - mammalian cells KW - DNA replication KW - DOT1 KW - protein KW - transcription KW - cultivation Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131449 VL - 40 IS - 20 ER - TY - JOUR A1 - Groeneweg, Femke L. A1 - van Royen, Martin E. A1 - Fenz, Susanne A1 - Keizer, Veer I. P. A1 - Geverts, Bart A1 - Prins, Jurrien A1 - de Kloet, E. Ron A1 - Houtsmuller, Adriaan B. A1 - Schmidt, Thomas S. A1 - Schaaf, Marcel J. M. T1 - Quantitation of Glucocorticoid Receptor DNA-Binding Dynamics by Single-Molecule Microscopy and FRAP JF - PLOS ONE N2 - Recent advances in live cell imaging have provided a wealth of data on the dynamics of transcription factors. However, a consistent quantitative description of these dynamics, explaining how transcription factors find their target sequences in the vast amount of DNA inside the nucleus, is still lacking. In the present study, we have combined two quantitative imaging methods, single-molecule microscopy and fluorescence recovery after photobleaching, to determine the mobility pattern of the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR), two ligand-activated transcription factors. For dexamethasone-activated GR, both techniques showed that approximately half of the population is freely diffusing, while the remaining population is bound to DNA. Of this DNA-bound population about half the GRs appeared to be bound for short periods of time (similar to 0.7 s) and the other half for longer time periods (similar to 2.3 s). A similar pattern of mobility was seen for the MR activated by aldosterone. Inactive receptors (mutant or antagonist-bound receptors) show a decreased DNA binding frequency and duration, but also a higher mobility for the diffusing population. Likely, very brief (<= 1 ms) interactions with DNA induced by the agonists underlie this difference in diffusion behavior. Surprisingly, different agonists also induce different mobilities of both receptors, presumably due to differences in ligand-induced conformational changes and receptor complex formation. In summary, our data provide a consistent quantitative model of the dynamics of GR and MR, indicating three types of interactions with DNA, which fit into a model in which frequent low-affinity DNA binding facilitates the search for high-affinity target sequences. KW - NF-KAPPA-B KW - image correlation spectroscopy KW - human mineralocorticoid receptor KW - nuclear-pore complexes KW - in-vivo KW - living cells KW - mobility KW - transcription KW - protein KW - reveals Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117085 VL - 9 IS - 3 ER - TY - JOUR A1 - Franke, Werner W. A1 - Scheer, Ulrich A1 - Trendelenburg, Michael F. A1 - Spring, Herbert A1 - Zentgraf, Hanswalter T1 - Absence of nucleosomes in transcriptionally active chromatin N2 - The ultrastructure of twO kinds of transcription ally active chromatin, the lampbrush chromosome loops and the nucleoli from amphibian oocytes and primary nuclei of the green alga Acetabularia, has been examined after manual isolation and dispersion in low salt media of slightly alkaline pH using various electron microscopic staining techniques (positive staining, metal shadowing, negative staining, preparation on positively charged films, etc.) and compared with the appearance of chromatin from various somatic cells (hen erythrocytes, rat hepatocytes, ClIltured murine sarcoma cells) prepared in parallel. While typical nucleosomes were revealed with all the techniques for chromatin from the latter three cell system, no nucleosomes were identified in either the lampbrush chromosome structures or the nucleolar chromatin. Nucleosomal arrays were absent not only in maximally fibril-covered matrix units but also in fibril-free regions between transcriptional complexes, including the apparent spacer intercepts between different transcriptional units. Moreover, comparisons of the length of the repeating units of rDNA in the transcribed state with those determined in the isolated rDNA and with the lengths of the first stable product of rDNA transcription, the pre-rRNA, demonstrated that the transcribed rDNA was not significantly shortened and/or condensed but rather extended in the transcriptional units. Distinct granules of about nucleosomal size which were sometimes found in apparent spacer regions as well as within matrix units of reduced fibril density were shown not to represent nucleosomes since their number per spacer unit was not inversely correlated with the length of the specific unit and also on the basis of their resistance to treatment with the detergent Sarkosyl NL-30. It is possible to structurally distinguish between transcriptionally active chromatin in which the DNA is extended in a non-nucleosomal form of chromatin and condensed, inactive chromatin within the typical nucleosomal package. The characteristic extended structure of transcriptionally active chromatin is found not only in the transcribed genes but also in non-transcribed regions within or between ("spacer") transcriptional units as well as in transcriptional units that are untranscribed amidst transcribed ones and/or have been inactivated for relatively short time. It is hypothesized that activation of transcription involves a transition from a nucleosomal to an extended chromatin organisation and that this structural transition is not specific for single "activated" genes but may involve larger chromatin regions, including adjacent untranscribed intercepts. KW - Cytologie KW - Chromatin structure KW - nucleosomes KW - transcription KW - electron microscopy Y1 - 1976 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-40646 ER - TY - JOUR A1 - Spring, Herbert A1 - Trendelenbrug, Michael F. A1 - Scheer, Ulrich A1 - Franke, Werner W. A1 - Herth, Werner T1 - Structural and biochemical studies of the primary nucleus of two green algal species, Acetabularia mediterranea and Acetabularia major N2 - Primary (giant) nuclei of the green algae Acetabularia mediterranea and A. major were studied by light and electron microscopy using in situ fixed material as well as manually isolated nuclear components. In addition, cytochemical reactions of nuclear structures and biochemical determinations of nuclear and cytoplasmic RNA and of genome DNA content were performed. The data obtained and the structures observed are interpreted as demonstralions of transcriptional activities of different gene classes. The most prominent class is the nucleolar cistrons of precursors of ribosomal RNA which occur highly repeated in clusters in the form of regularly alternating intercepts on deoxyribonucleoprotein axes of transcribed rDNA, the fibril-covered matrix units, and the fibril-free "spacer" segments. A description and a classification of the various structural complexes which seem to represent transcriptional activities is given. Quantitative evaluations of these arrangements are presented. The morphology and the dimensions of such structures are compared with the RNA molecular weight determinations and with the corresponding data reported from various animal cell systems. It is suggested that the formation of the giant nucleus is correlated with, and probably due to, an enormous amplification of transcriptionally active rDNA and packing of the extrachromosomal copies into the large nucleolar aggregate bodies. KW - Cytologie KW - Nucleolus KW - electron microscopy KW - Acetabularia KW - transcription KW - gene activity KW - ribosomes Y1 - 1974 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-40600 ER - TY - THES A1 - Schmit, Fabienne T1 - LINC, a novel protein complex involved in the regulation of G2/M genes T1 - LINC, ein neuer Proteinkomplex, der G2/M Gene reguliert N2 - Regulated progression through the cell cycle is essential for ordered cell proliferation. One of the best characterized tumor suppressors is the retinoblastoma protein pRB, which together with the E2F transcription factors regulates cell cycle progression. In the model organisms Drosophila melanogaster and Caenorhabditis elegans, RB/E2F containing multiprotein complexes have been described as transcriptional regulators of gene expression. This work first describes a homologous complex in human cells named LINC (for LIN complex). It consists of a stable core complex containing LIN-9, LIN-37, LIN-52, LIN-54 and RbAp48. This core complex interacts cell cycle-dependently with different pocket proteins and transcription factors. In quiescent cells, LINC associates with p130 and E2F4. In S-phase cells these interactions are lost and LINC binds to B-MYB and p107. The transient knock-down of LIN-54 in primary fibroblasts, as the depletion of LIN-9, leads to cell cycle defects. The cells are delayed before the entry into mitosis. This effect is due to the fact that the knock-down of LINC components leads to the downregulation of cell cycle genes responsible for the entry into and exit from mitosis as well as for checkpoints during mitosis. These LINC target genes are known E2F G2/M target genes, which are expressed later than the classical G1/S E2F target genes. The transcriptional regulation by LINC is a direct effect as LINC binds to the promoters of its target genes throughout the cell cycle. LINC contains three DNA-binding proteins. E2F4 and B-MYB, which cell cycle-dependently bind to LINC, are known DNA-binding transcription factors. Additionally, it is show here that the LINC core complex member LIN-54 also directly binds to the promoter of a LINC target gene. Although the exact molecular mechanism of LINC function needs to be analyzed further, data in this work provide a model for the delayed activation of G2/M target genes. B-MYB, a G1/S E2F target gene, binds to LINC upon its expression in S-phase. Then only LINC is a transcriptional activator that induces the expression of the G2/M genes. This provides an explanation for the delayed expression of these E2F G2/M target genes. N2 - Die Regulation des Zellzyklus ist unerlässlich für die fehlerfreie Zellteilung. Einer der am Besten charakterisierten Tumorsuppressoren ist das Retinoblastom-Protein pRB, welches zusammen mit den E2F Transkriptionsfaktoren den Zellzyklus reguliert. In den Modellorganismen Drosophila melanogaster und Caenorhabditis elegans wurden Multiproteinkomplexe beschrieben, die pRB und E2F Homologe enthalten und transkriptionell die Expression von Zielgenen regulieren. Diese Arbeit beschreibt erstmals LINC, einen homologen Komplex in humanen Zellen. Der LIN-Kernkomplex besteht aus LIN-9, LIN-37, LIN-52, LIN-54 and RbAp48 und assoziiert zellzyklus-abhängig mit Pocket Proteinen und Transkriptionsfaktoren. In ruhenden Zellen (G0) assoziiert LINC mit p130 und E2F4. In der S-Phase verlassen p130 und E2F4 den Komplex und B-MYB und p107 interagieren mit LINC. Die transiente Depletion von LIN-54, ebenso wie die Depletion von LIN-9, führt zu Defekten im Zellzyklus. Die „knock-down“-Zellen treten verzögert in die Mitose ein. Dies konnte darauf zurückgeführt werden, dass die Depletion von LINC Mitgliedern Gene herunterreguliert, die für den Eintritt in und den Austritt aus der Mitose, sowie für Regulationsprozesse während der Mitose verantwortlich sind. Diese LINC Zielgene wurden bisher als G2/M E2F Zielgene beschrieben, welche verglichen mit klassischen E2F Zielgenen verzögert exprimiert werden. Die transkriptionelle Regulation durch LINC ist ein direkter Effekt, da LINC in G0 und in der S-Phase an die Promotoren seiner Zielgene bindet. LINC enthält drei DNA-bindende Proteine. Die zellzyklus-abhängigen Komponenten von LINC E2F4 und BMYB sind bekannte DNA-bindende Transkriptionsfaktoren. Zusätzlich konnte in dieser Arbeit gezeigt werden, dass das LINC Kernprotein LIN-54 direkt an den Promoter eines LINC Zielgens, cdc2, bindet. Obwohl der genaue molekulare Mechanismus für die Funktion von LINC noch genauer untersucht werden muss, liefern Daten in dieser Arbeit ein Modell für die verzögerte Expression von G2/M Genen. B-MYB ist selbst ein E2F Zielgen und bindet an LINC sobald es exprimiert wird. Erst die Assoziation von B-MYB an LINC in der S-Phase macht LINC zu einem transkriptionellen Aktivator G2/M-spezifischer Gene. Dies erklärt die verzögerte Expression dieser E2F G2/M Zielgene. KW - Zellzyklus KW - Transkription KW - LINC KW - LIN-54 KW - G2/M Übergang KW - LINC KW - LIN-54 KW - cell cycle KW - G2/M transition KW - transcription Y1 - 2008 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-29336 ER -