Noncoding Elements: Evolution and Epigenetic Regulation

Handle URI:
http://hdl.handle.net/10754/603694
Title:
Noncoding Elements: Evolution and Epigenetic Regulation
Authors:
Seridi, Loqmane ( 0000-0001-7028-3024 )
Abstract:
When the human genome project was completed, it revealed a surprising result. 98% of the genome did not code for protein of which more than 50% are repeats— later known as ”Junk DNA”. However, comparative genomics unveiled that many noncoding elements are evolutionarily constrained; thus luckily to have a role in genome stability and regulation. Though, their exact functions remained largely unknown. Several large international consortia such as the Functional Annotation of Mammalian Genomes (FANTOM) and the Encyclopedia of DNA Elements (ENCODE) were set to understand the structure and the regulation of the genome. Specifically, these endeavors aim to measure and reveal the transcribed components and functional elements of the genome. One of the most the striking findings of these efforts is that most of the genome is transcribed, including non-conserved noncoding elements and repeat elements. Specifically, we investigated the evolution and epigenetic properties of noncoding elements. 1. We compared genomes of evolutionarily distant species and showed the ubiquity of constrained noncoding elements in metazoa. 2. By integrating multi-omic data (such as transcriptome, nucleosome profiling, histone modifications), I conducted a comprehensive analysis of epigenetic properties (chromatin states) of conserved noncoding elements in insects. We showed that those elements have distinct and protective sequence features, undergo dynamic epigenetic regulation, and appear to be associated with the structural components of the chromatin, replication origins, and nuclear matrix. 3. I focused on the relationship between enhancers and repetitive elements. Using Cap Analysis of Gene Expression (CAGE) and RNASeq, I compiled a full catalog of active enhancers (a class of noncoding elements) during myogenesis of human primary cells of healthy donors and donors affected by Duchenne muscular dystrophy (DMD). Comparing the two time-courses, a significant change in the epigenetic landscape in DMD was observed that lead to global dysregulation of enhancers and associated repetitive elements.
Advisors:
Ravasi, Timothy ( 0000-0002-9950-465X )
Committee Member:
Gao, Xin ( 0000-0002-7108-3574 ) ; Orlando, Valerio; Carnici, Piero
KAUST Department:
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division; Computer Science
Program:
Computer Science
Issue Date:
9-Mar-2016
Type:
Dissertation
Appears in Collections:
Dissertations; Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.advisorRavasi, Timothyen
dc.contributor.authorSeridi, Loqmaneen
dc.date.accessioned2016-03-27T12:10:23Zen
dc.date.available2016-03-27T12:10:23Zen
dc.date.issued2016-03-09en
dc.identifier.urihttp://hdl.handle.net/10754/603694en
dc.description.abstractWhen the human genome project was completed, it revealed a surprising result. 98% of the genome did not code for protein of which more than 50% are repeats— later known as ”Junk DNA”. However, comparative genomics unveiled that many noncoding elements are evolutionarily constrained; thus luckily to have a role in genome stability and regulation. Though, their exact functions remained largely unknown. Several large international consortia such as the Functional Annotation of Mammalian Genomes (FANTOM) and the Encyclopedia of DNA Elements (ENCODE) were set to understand the structure and the regulation of the genome. Specifically, these endeavors aim to measure and reveal the transcribed components and functional elements of the genome. One of the most the striking findings of these efforts is that most of the genome is transcribed, including non-conserved noncoding elements and repeat elements. Specifically, we investigated the evolution and epigenetic properties of noncoding elements. 1. We compared genomes of evolutionarily distant species and showed the ubiquity of constrained noncoding elements in metazoa. 2. By integrating multi-omic data (such as transcriptome, nucleosome profiling, histone modifications), I conducted a comprehensive analysis of epigenetic properties (chromatin states) of conserved noncoding elements in insects. We showed that those elements have distinct and protective sequence features, undergo dynamic epigenetic regulation, and appear to be associated with the structural components of the chromatin, replication origins, and nuclear matrix. 3. I focused on the relationship between enhancers and repetitive elements. Using Cap Analysis of Gene Expression (CAGE) and RNASeq, I compiled a full catalog of active enhancers (a class of noncoding elements) during myogenesis of human primary cells of healthy donors and donors affected by Duchenne muscular dystrophy (DMD). Comparing the two time-courses, a significant change in the epigenetic landscape in DMD was observed that lead to global dysregulation of enhancers and associated repetitive elements.en
dc.language.isoenen
dc.subjectnon-coding elementsen
dc.subjectconserved elementsen
dc.subjectenhancersen
dc.subjectenhancers RNAsen
dc.subjectrepeat elementsen
dc.subjectepigeneticsen
dc.titleNoncoding Elements: Evolution and Epigenetic Regulationen
dc.typeDissertationen
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.contributor.departmentComputer Scienceen
thesis.degree.grantorKing Abdullah University of Science and Technologyen_GB
dc.contributor.committeememberGao, Xinen
dc.contributor.committeememberOrlando, Valerioen
dc.contributor.committeememberCarnici, Pieroen
thesis.degree.disciplineComputer Scienceen
thesis.degree.nameDoctor of Philosophyen
dc.person.id101821en
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