Assessing the relationship between chromatin and splicing factors in alternative splicing
Proteins that bind to DNA or RNA are both known to influence alternative splicing. However, there has not been so far a systematic experimental exploration of the relationship between these factors in their effect on splicing. In this thesis, we make use of the large amounts of publicly available hi...
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| Formato: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2015 |
| País: | España |
| Recursos: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/316790 |
| Acesso em linha: | http://hdl.handle.net/10803/316790 |
| Access Level: | acceso abierto |
| Palavra-chave: | Alternative splicing Chromatin Sequencing Motifs CTCF Empalmament alternatiu Cromatina Seqüenciació Motius 575 |
| Resumo: | Proteins that bind to DNA or RNA are both known to influence alternative splicing. However, there has not been so far a systematic experimental exploration of the relationship between these factors in their effect on splicing. In this thesis, we make use of the large amounts of publicly available high throughput sequencing data that now make it possible to explore this question on a genome-wide scale. We made exhaustive use of a method known as profiling to address this question. As most profiling methods in common use are merely qualitative, the first task of the thesis was to generate a quantitative profiling method and bioinformatics tool, ProfileSeq, which we validated by reproducing previous results from the literature. ProfileSeq and other methods were combined to mine for relationships between DNA and RNA binding factors with potential relevance to splicing. We found significant associations between the transcription factor CTCF and the RNA binding protein LIN28A, and similarly between SPI1 and RNA-binding proteins that bind to AC-rich motifs, such as hnRNPL. These represent putative relationships relevant to splicing, as these results were reached by more than one independent method with independent datasets. We also show evidence that CTCF acts as a barrier between regions of H3K4me3 marking inside genes. A number of other results of potential interest to both the bioinformatics and molecular biology communities are also described |
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