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postgraduate thesis: Bioinformatics analysis of genetic and epigenetic factors regulating gene expression

TitleBioinformatics analysis of genetic and epigenetic factors regulating gene expression
Authors
Issue Date2015
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Wang, Y. [王嫣]. (2015). Bioinformatics analysis of genetic and epigenetic factors regulating gene expression. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5387960
AbstractGene transcription is a fundamental and important step for cellular function, biological process and pathogenesis. The diversified temporal and spatial patterns of gene expression are complicated and how they are controlled remains not completely understood. Therefore, the regulation mechanism behind transcription is gaining increasing interest and focus. The process of transcription is controlled by multiple factors in a sophisticated system, including functional DNA sequences, DNA binding proteins and chromosome conformation. In this study, bioinformatics methods are employed to explore the characteristics and patterns of cis-regulatory elements, trans-acting factors and the interactions among them in specific epigenetic environment, all involved in the gene expression regulation mechanism. Cis-regulatory elements include promoters and other distant ones, such as enhancers. In this study promoters are categorized based on transcript type, transcription direction or genes’ tissue specificity, and compared based on their genetic and epigenetic features. It is found the intrinsic features of promoter sequence, including CpG island frequency, general transcription factor binding motifs and sequence conservation, are more correlated with transcript type and transcription direction, while the tissue specific gene expression pattern is more affected by the trans-acting proteins and epigenetic environment, including DNA methylation and histone modification. For enhancers, the focus in this study is on their detection, data curation and target gene finding. Detection methods to date are reviewed and validated human enhancers are recorded. Furthermore, with available long-range chromatin interaction data, distant enhancer targets are inferred. Finally a database named EATdb is presented for users to search enhancers and enhancer targets. Trans-acting factors function cooperatively with cis-regulatory elements, and they are indispensable components of the regulatory network. In this study, Hi-C data are analyzed to understand how trans-acting factors assist in forming chromosome conformation and the long-range regulation system. The study combining transcription factor binding peaks and long-range chromatin interaction data discloses that some tissue specific transcription factors are crucial to the chromosome conformation. All interactions among cis-regulatory elements and trans-acting factors occur in specific epigenetic environment, so various histone modifications’ patterns in promoter regions, chromatin interactions and the whole genome are examined and compared in different cells. The knowledge that histone modifications could increase or decrease gene expression is confirmed and some novel observations are reported. On the basis of this knowledge a web server named EpiRegNet is built for public use on detecting important histone modifications affecting the expression of a given set of genes. In general, this study consists of several aspects of the research on gene expression regulation and discovers several findings concerning the regulation mechanism. Cis-regulatory elements and trans-acting factors are first studied independently to understand their roles in affecting gene expression, and then analyzed together in an integrated system to explore the regulation mechanism. Meanwhile, epigenetic factors are taken into consideration through all parts of the study. In conclusion, this study provides a comprehensive view of the gene expression regulation mechanism and is hopefully useful for similar research.
DegreeDoctor of Philosophy
SubjectGene expression
Dept/ProgramBiochemistry
Persistent Identifierhttp://hdl.handle.net/10722/222277

 

DC FieldValueLanguage
dc.contributor.authorWang, Yan-
dc.contributor.author王嫣-
dc.date.accessioned2016-01-09T18:09:24Z-
dc.date.available2016-01-09T18:09:24Z-
dc.date.issued2015-
dc.identifier.citationWang, Y. [王嫣]. (2015). Bioinformatics analysis of genetic and epigenetic factors regulating gene expression. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5387960-
dc.identifier.urihttp://hdl.handle.net/10722/222277-
dc.description.abstractGene transcription is a fundamental and important step for cellular function, biological process and pathogenesis. The diversified temporal and spatial patterns of gene expression are complicated and how they are controlled remains not completely understood. Therefore, the regulation mechanism behind transcription is gaining increasing interest and focus. The process of transcription is controlled by multiple factors in a sophisticated system, including functional DNA sequences, DNA binding proteins and chromosome conformation. In this study, bioinformatics methods are employed to explore the characteristics and patterns of cis-regulatory elements, trans-acting factors and the interactions among them in specific epigenetic environment, all involved in the gene expression regulation mechanism. Cis-regulatory elements include promoters and other distant ones, such as enhancers. In this study promoters are categorized based on transcript type, transcription direction or genes’ tissue specificity, and compared based on their genetic and epigenetic features. It is found the intrinsic features of promoter sequence, including CpG island frequency, general transcription factor binding motifs and sequence conservation, are more correlated with transcript type and transcription direction, while the tissue specific gene expression pattern is more affected by the trans-acting proteins and epigenetic environment, including DNA methylation and histone modification. For enhancers, the focus in this study is on their detection, data curation and target gene finding. Detection methods to date are reviewed and validated human enhancers are recorded. Furthermore, with available long-range chromatin interaction data, distant enhancer targets are inferred. Finally a database named EATdb is presented for users to search enhancers and enhancer targets. Trans-acting factors function cooperatively with cis-regulatory elements, and they are indispensable components of the regulatory network. In this study, Hi-C data are analyzed to understand how trans-acting factors assist in forming chromosome conformation and the long-range regulation system. The study combining transcription factor binding peaks and long-range chromatin interaction data discloses that some tissue specific transcription factors are crucial to the chromosome conformation. All interactions among cis-regulatory elements and trans-acting factors occur in specific epigenetic environment, so various histone modifications’ patterns in promoter regions, chromatin interactions and the whole genome are examined and compared in different cells. The knowledge that histone modifications could increase or decrease gene expression is confirmed and some novel observations are reported. On the basis of this knowledge a web server named EpiRegNet is built for public use on detecting important histone modifications affecting the expression of a given set of genes. In general, this study consists of several aspects of the research on gene expression regulation and discovers several findings concerning the regulation mechanism. Cis-regulatory elements and trans-acting factors are first studied independently to understand their roles in affecting gene expression, and then analyzed together in an integrated system to explore the regulation mechanism. Meanwhile, epigenetic factors are taken into consideration through all parts of the study. In conclusion, this study provides a comprehensive view of the gene expression regulation mechanism and is hopefully useful for similar research.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.subject.lcshGene expression-
dc.titleBioinformatics analysis of genetic and epigenetic factors regulating gene expression-
dc.typePG_Thesis-
dc.identifier.hkulb5387960-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplineBiochemistry-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b5387960-

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