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dc.contributor.advisorKhalil, Ahmad S.en_US
dc.contributor.authorPark, Minheeen_US
dc.date.accessioned2019-09-23T19:12:46Z
dc.date.issued2019
dc.identifier.urihttps://hdl.handle.net/2144/37984
dc.description.abstractChromatin is decorated by a large array of biochemical modifications made to DNA and histone proteins. These modifications—and the broader organizational structure of chromatin—provide an important additional layer of information that is superimposed upon genome sequence and thus are widely referred to as the epigenome. The epigenome helps control which genes are expressed in a given context to produce the gene expression patterns that underlie the many different cellular phenotypes that arise during an organism’s development, and determine how these gene expression patterns are subsequently maintained for the life of an organism. The epigenetically heritable states are maintained and transmitted by self-propagating epigenetic mechanisms that persist in the absence of an initial stimulus. These epigenetic programs are generally thought to be controlled by core regulatory networks involving molecular writers and readers of chromatin marks. Guided by these principles, in this dissertation, we establish an orthogonal epigenetic regulatory system in mammalian cells using N6-methyladenine (m6A), a DNA modification not commonly found in metazoan epigenomes. Our system consists of synthetic factors that can write and read m6A, and consequently recruit transcriptional regulators to control reporter loci. Inspired by models of chromatin spreading and epigenetic inheritance, we use our system and mathematical models to construct regulatory circuits that induce m6A-dependent transcriptional states, promote their spatial propagation, and maintain epigenetic memory of the states. These minimal circuits are able to program epigenetic functions de novo, conceptually validating “read-write” architectures. This dissertation outlines a synthetic framework for investigating models of epigenetic regulation and encoding additional layers of epigenetic information in cells.en_US
dc.language.isoen_US
dc.subjectBiomedical engineeringen_US
dc.subjectCell engineeringen_US
dc.subjectChromatinen_US
dc.subjectDNA methylationen_US
dc.subjectEpigeneticsen_US
dc.subjectGene regulationen_US
dc.subjectSynthetic biologyen_US
dc.titleEngineering a synthetic epigenetic systemen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2019-08-30T19:04:12Z
dc.description.embargo2021-08-30T00:00:00Z
etd.degree.nameDoctor of Philosophyen_US
etd.degree.leveldoctoralen_US
etd.degree.disciplineBiomedical Engineeringen_US
etd.degree.grantorBoston Universityen_US
dc.identifier.orcid0000-0002-2101-5485


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