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Interacciones entre activadores y represores en el inicio de la transcripción en Saccharomyces cerevisiae

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Interacciones entre activadores y represores en el inicio de la transcripción en Saccharomyces cerevisiae

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dc.contributor.advisor Estruch Ros, Francisco es_ES
dc.contributor.author Peiró Chova, Lorena es_ES
dc.contributor.other Universitat de València. Departament de Bioquímica i Biologia Molecular es_ES
dc.date.accessioned 2012-04-19T18:06:16Z
dc.date.available 2012-04-19T18:06:16Z
dc.date.issued 2010 es_ES
dc.date.submitted 2010-06-04 es_ES
dc.identifier.isbn isbn:9788437079431 es_ES
dc.identifier.uri http://hdl.handle.net/10803/52091 es_ES
dc.identifier.uri http://hdl.handle.net/10550/23419
dc.description.abstract Autosomic dominant lateral temporal epilepsy (ADLTE) is a form of partial epilepsy with secondary generalized seizures, caused by mutations in LGI1. This gene was initially identified in 1998, as a tumour suppressor in multiform glioblastoma, affecting to the malignancy of these tumours. In silico analysis of the primary sequence of LGI1, revealed four paralogues of the gene, which shared a very similar domain structure and were named as LGI1, LGI2, LGI3 and LGI4. The existence of similar types of epilepsy with common features for that seen for ADLTE, suggests that some other members of this gene family could be involved in these pathologies. Moreover, the presence of four paralogues, makes the idea of a certain degree of functional redundancy, possible. This fact, could be explained by the complementary distribution of cells expressing the genes of this family in the brain. In this work, we show a detailed expression analysis of the mRNA of the members of the LGI family in adult mouse brain. The distribution of these genes is regionally heterogeneous, suggesting that since their origin as a common ancestral gene, a subfunctionalization might have occurred. In this work, we try to shed light on these possible functions. es_ES
dc.description.abstract Negative cofactor 2 (NC2) has been described as an essential and evolutionarily conserved transcriptional repressor, although in vitro and in vivo experiments suggest that it can function as both a positive and a negative effector of transcription. NC2 operates by interacting with the core promoter and components of the basal transcription machinery, like the TBP. In this work, we have isolated mutants that suppress the growth defect caused by depletion of NC2. We have identified mutations affecting components of three different complexes involved in the control of basal transcription: the mediator, TFIIH, and RNA pol II itself. Mutations in RNA pol II include both overexpression of truncated forms of the two largest subunits (Rpb1p and Rpb2p) and reduced levels of these proteins. Suppression of NC2 depletion was also observed by reducing the amounts of the mediator essential components Nut2p and Med7p, as well as by deleting any of the nonessential mediator components, except Med2p, Med3p, and Gal11p subunits. Interestingly, the Med2p/Med3p/Gal11p triad forms a submodule within the mediator tail. Our results support the existence of different components within the basic transcription complexes that antagonistically interact with NC2 repressor and suggest that the correct balance between the activities of specific positive and negative components is essential for cell growth. In the second part of this work, we study a novel and highly conserved factor that physically interacts with most of the RNA pol II subunits, Iwr1p. Here we show that Iwr1p genetically interacts with components of the basal transcription machinery and plays a role in both basal and regulated transcription. We report that mutation of IWR1 gene is able to bypass the otherwise essential requirement for the transcriptional regulator NC2, which occurs with different components of the basal transcription machinery, including TFIIA and subunits of the mediator complex. Deletion of the IWR1 gene leads to an altered expression of specific genes, including phosphate-responsive genes and SUC2. Our results show that Iwr1p is a nucleocytoplasmic shuttling protein and suggest that Iwr1p acts early in the formation of the pre-initiation complex by mediating the interaction of certain activators with the basal transcription apparatus. es_ES
dc.format.extent 233 p. es_ES
dc.language spa es_ES
dc.subject Facultat de Biològiques es_ES
dc.subject Bioquímica. Biologia molecular. Biofísica es_ES
dc.title Interacciones entre activadores y represores en el inicio de la transcripción en Saccharomyces cerevisiae es_ES
dc.type doctoral thesis es_ES
dc.type.hasVersion VoR es_ES

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