Noncoding Elements: Evolution and Epigenetic Regulation

الموضوعات

علوم تطبيقية وتكنولوجية

الملخص

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.

روابط وملفات

التعريف والنوع

رقم الوثيقة

0c614491-1633-4a1a-aec6-56ef3c2cdfbd

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل دكتوراة

نوع الملف

pdf text

أسماء الملفات

1699952_1.pdf

بيانات النشر

ألقاب المؤلفين

[{"name_ar":"تيموثي رافاسي","title_ar":"اشراف","title_en":"Supervision"},{"name_ar":"لقمان سيريدي","title_ar":"اعداد","title_en":"Preparation"}]

اللغة

English

المصدر والدورية

اسم المصدر

Noncoding Elements: Evolution and Epigenetic Regulation

المحتوى والصفحات

عدد الصفحات

0

كلمات الباحثين

conserved elements , enhancers RNAs , enhancers , epigenetics , non-coding elements , repeat elements

إشراف وإعداد

الإشراف

تيموثي رافاسي

الإعداد

لقمان سيريدي

الاقتباسات الببليوغرافية