A binary combinatorial histone code
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School of Science |
Master's thesis
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Date
2012
Department
Major/Subject
Informaatiotekniikka
Mcode
T-61
Degree programme
Language
en
Pages
x + 59 s.
Series
Abstract
Background: Post-translational modifications of nucleosomal histone proteins play a vital role in regulation of gene expression, and are considered as one of the major emerging concept to study gene regulation. But a comprehensive study of combinatorial patterns, or networks, of the post-translational histone modifications within nucleosomes still remains limited. Methods and Results: In this thesis, we describe a framework to identify histone modification networks that might exist within nucleosomes. To test this framework, we combined ChIP-seq data from human CD4+ T cells covering 39 different histone modifications, and identified over 750,000 nucleosomes. We then carried out Boolean association analysis for top 186,000 nucleosomes for each individual histone modification, and robustly searched to find which other modifications show best dependency. We then identified most prominent histone modification combination that occurred among the selected modifications. Conclusions: Our results provide a comprehensive list of combinatorial patterns of histone modifications that might exist together within nucleosomes. We conclude that Boolean approach provides a computationally efficient way to study histone modification networks. We believe that when this approach is extended to different regulatory regions, such as enhancers and insulators, will provide us with better insights into gene regulation.Description
Supervisor
Lähdesmäki, HarriThesis advisor
Lähdesmäki, HarriKeywords
histone modifications, nucleosomes, chromatin, gene regulation, regulatory elements, ChIP-Seq data, boolean models, feature selection, network selection