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dc.contributor.advisorRichard A. Young.en_US
dc.contributor.authorFan, Zi Pengen_US
dc.contributor.otherMassachusetts Institute of Technology. Computational and Systems Biology Program.en_US
dc.date.accessioned2015-09-17T19:01:39Z
dc.date.available2015-09-17T19:01:39Z
dc.date.copyright2015en_US
dc.date.issued2015en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/98641
dc.descriptionThesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2015.en_US
dc.descriptionCataloged from PDF version of thesis.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstractMammals contain a wide array of cell types with distinct functions, yet nearly all cell types have the same genomic DNA. How the genetic instructions in DNA are selectively interpreted by cells to specify various cellular functions is a fundamental question in biology. This thesis work describes two genome-wide studies designed to study how transcriptional control of gene expression programs defines cell identity. Recent studies suggest that a small number of transcription factors, called "master" transcription factors, dominate the control of gene expression programs. These master transcription factors and the transcriptional regulatory circuitry they produce, however, are not known for all cell types. Ectopic expression of these factors can, in principle, direct transdifferentiation of readily available cells into medically relevant cell types for applications in regenerative medicine. Limited knowledge of these factors is a roadblock to generation of many medically relevant cell types. Chapter 2 presents a study in which a novel computational approach was undertaken to generate an atlas of candidate master transcriptional factors for 100+ human tissue/cell types. The candidate master transcription factors in retinal pigment epithelial (RPE) cells were then used to guide the investigation of the regulatory circuitry of RPE cells and to reprogram human fibroblasts into functional RPE-like cells. Master transcription factors define cell-type-specific gene expression through binding to enhancer elements in the genome. These enhancer-bound transcription factors regulate genes by contacting target gene promoters via the formation of DNA loops. It is becoming increasingly clear that transcription factors operate and regulate gene expression within a larger three-dimensional (3D) chromatin architecture, but these structures and their functions are poorly understood. Chapter 3 presents a study in which Cohesin ChIA-PET data was generated to identify the local chromosomal structures at both active and repressed genes across the genome in embryonic stem cells. The results led to the discovery of functional insulated neighborhood structures that are formed by two CTCF interaction sites occupied by Cohesin. The integrity of these looped structures contributes to the transcriptional control of super-enhancer-driven active genes and repressed genes encoding lineage-specifying developmental regulators.en_US
dc.description.statementofresponsibilityby Zi Peng Fan.en_US
dc.format.extent219 pagesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsM.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.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectComputational and Systems Biology Program.en_US
dc.titleTranscriptional and structural control of cell identity genesen_US
dc.typeThesisen_US
dc.description.degreePh. D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Computational and Systems Biology Program
dc.identifier.oclc920678090en_US


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