EPIGENOMIC SIGNATURES OF NEURONAL DIVERSITY IN THE MAMMALIAN BRAIN

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dc.contributor.advisorBlackshaw, Seth
dc.contributor.committeeMemberSong, Hongjun
dc.contributor.committeeMemberWheelan, Sarah J.
dc.creatorMo, Alisa
dc.date.accessioned2018-10-03T02:43:01Z
dc.date.available2018-10-03T02:43:01Z
dc.date.created2017-05
dc.date.issued2015-04-24
dc.date.submittedMay 2017
dc.date.updated2018-10-03T02:43:01Z
dc.description.abstractNeuronal diversity is essential for mammalian brain function but poses a challenge to molecular profiling. To address the need for tools that facilitate cell type-specific epigenomic studies, we developed the first affinity purification approach to isolate nuclei from genetically-defined cell types in a mammal. We combine this technique with next generation sequencing to show that three subtypes of neocortical neurons have highly distinctive epigenomic landscapes. Over 200,000 regions differ in chromatin accessibility and DNA methylation signatures characteristic of gene regulatory regions. By footprinting and motif analyses, these regions are predicted to bind distinct cohorts of neuron subtype-specific transcription factors. Neuronal epigenomes reflect both past and present gene expression, with DNA hyper-methylation at developmentally critical genes appearing as a novel epigenomic signature in mature neurons. Taken together, our findings link the functional and transcriptional complexity of neurons to their underlying epigenomic diversity.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://jhir.library.jhu.edu/handle/1774.2/59309
dc.language.isoen_US
dc.publisherJohns Hopkins University
dc.publisher.countryUSA
dc.subjectneurons
dc.subjectDNA methylation
dc.subjectchromatin
dc.titleEPIGENOMIC SIGNATURES OF NEURONAL DIVERSITY IN THE MAMMALIAN BRAIN
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentNeuroscience
thesis.degree.disciplineNeuroscience
thesis.degree.grantorJohns Hopkins University
thesis.degree.grantorSchool of Medicine
thesis.degree.levelDoctoral
thesis.degree.namePh.D.
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