Genome regulation by long noncoding RNAs
Thesis: Ph. D. in Bioinformatics and Integrative Genomics, Harvard-MIT Program in Health Sciences and Technology, 2016.
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | eng |
| Published: |
Massachusetts Institute of Technology
2016
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/1721.1/104616 |
| _version_ | 1810995110586875904 |
|---|---|
| author | Engreitz, Jesse M. (Jesse Michael) |
| author2 | Eric S. Lander. |
| author_facet | Eric S. Lander. Engreitz, Jesse M. (Jesse Michael) |
| author_sort | Engreitz, Jesse M. (Jesse Michael) |
| collection | MIT |
| description | Thesis: Ph. D. in Bioinformatics and Integrative Genomics, Harvard-MIT Program in Health Sciences and Technology, 2016. |
| first_indexed | 2024-09-23T13:52:04Z |
| format | Thesis |
| id | mit-1721.1/104616 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T13:52:04Z |
| publishDate | 2016 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/1046162019-04-10T07:51:02Z Genome regulation by long noncoding RNAs Genome regulation by lncRNAs Genome regulation by long noncoding Ribonucleic acids Engreitz, Jesse M. (Jesse Michael) Eric S. Lander. Harvard--MIT Program in Health Sciences and Technology. Harvard--MIT Program in Health Sciences and Technology. Harvard--MIT Program in Health Sciences and Technology. Thesis: Ph. D. in Bioinformatics and Integrative Genomics, Harvard-MIT Program in Health Sciences and Technology, 2016. Cataloged from PDF version of thesis. Includes bibliographical references. Our genomes encode the molecular information that gives rise to life, yet we are just beginning to unravel how this information is organized, interpreted, and regulated. While the human genome contains -20,000 protein-coding genes, mammalian genomes also produce thousands of long non-coding RNAs (lncRNAs), some of which are now known to play essential roles in diverse biological processes including cellular differentiation and human disease. Recent studies show that many lncRNAs localize to the nucleus and interact with chromatin regulatory complexes, suggesting that some lncRNAs may represent a crucial missing component in our understanding of genome regulation. To test whether lncRNAs localize to and regulate specific sites in the genome, we developed genome-wide approaches to map lncRNA interactions with chromatin. Through studies of three conserved lncRNAs, we demonstrate that lncRNAs can exploit the three-dimensional architecture of the genome to identify their regulatory targets and, in turn, actively manipulate genome architecture to form subcompartments containing co-regulated genes. Thus, lncRNAs have unique capabilities as dynamic regulators that can locally amplify epigenetic signals. We next explored whether this model might apply to other long noncoding RNAs, many of which are not conserved across species and thus whose functions remain unclear. Through genetic dissection of their local regulatory functions, we show that many of these genomic loci participate in the local regulation of gene expression, but that these functions do not involve the IncRNA transcripts themselves. Instead, multiple mechanisms associated with RNA production including their promoters, the process of transcription, and RNA splicing - act in local networks of regulatory connections between spatially proximal genes, both protein-coding and noncoding. These findings reveal novel mechanistic explanations for the functions and evolution of noncoding transcription in mammalian genomes. Together these studies suggest a model in which mammalian gene regulation is organized into local neighborhoods defined by the spatial architecture of the genome. Within these neighborhoods, lncRNAs and DNA regulatory elements may function cooperatively to coordinate local gene expression. Dissecting this fundamental model for genome regulation may enable manipulation of the processes that interpret our genome sequence and galvanize efforts to develop new treatments for human disease. by Jesse M. Engreitz. Ph. D. in Bioinformatics and Integrative Genomics 2016-09-30T19:38:34Z 2016-09-30T19:38:34Z 2016 2016 Thesis http://hdl.handle.net/1721.1/104616 959009677 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 313 pages application/pdf Massachusetts Institute of Technology |
| spellingShingle | Harvard--MIT Program in Health Sciences and Technology. Engreitz, Jesse M. (Jesse Michael) Genome regulation by long noncoding RNAs |
| title | Genome regulation by long noncoding RNAs |
| title_full | Genome regulation by long noncoding RNAs |
| title_fullStr | Genome regulation by long noncoding RNAs |
| title_full_unstemmed | Genome regulation by long noncoding RNAs |
| title_short | Genome regulation by long noncoding RNAs |
| title_sort | genome regulation by long noncoding rnas |
| topic | Harvard--MIT Program in Health Sciences and Technology. |
| url | http://hdl.handle.net/1721.1/104616 |
| work_keys_str_mv | AT engreitzjessemjessemichael genomeregulationbylongnoncodingrnas AT engreitzjessemjessemichael genomeregulationbylncrnas AT engreitzjessemjessemichael genomeregulationbylongnoncodingribonucleicacids |