Show simple item record

dc.contributor.advisorIsaac S. Kohane.en_US
dc.contributor.authorHarmin, David Alan, 1954-en_US
dc.contributor.otherHarvard University--MIT Division of Health Sciences and Technology.en_US
dc.date.accessioned2008-12-11T18:31:40Z
dc.date.available2008-12-11T18:31:40Z
dc.date.copyright2008en_US
dc.date.issued2008en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/43811
dc.descriptionThesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology, 2008.en_US
dc.descriptionIncludes bibliographical references (p. 67-69).en_US
dc.description.abstractSeveral bioinformatic tools will be brought to bear in this thesis to identify specific genomic loci that serve as regulatory gateways of gene expression in brain. These "motifs" are short nucleotide patterns that occur in promoters and 5' or 3' untranslated regions of genes. Occurrences of motifs that function in eukaryotic genomes as, e.g., transcription factor binding sites or targets of RNA interference are assumed to lie at the nexus of several trends. Instances that are indeed regulatory and not just bits of random sequence should show evidence of actual binding of factors that have a significant effect on expression levels. Such motif instances are also expected to be significantly enriched (or de-enriched), compared to background, in the genes regulated by their binding factors and in brain structures most closely associated with these genes' functions. Finally, truly regulatory motif instances are likely to be highly conserved in orthologous genes across multiple genomes; i.e., conservation can be taken as a proxy for function. My research exploits these ideas by exploring genome-wide properties of motifs associated with the transcription factor family MEF2, some of whose members are known to play a role in synapse development. Data from chromatin immunoprecipitation and tiling-microarray (ChIP-on-chip) experiments [11 have isolated peaks of specific binding by MEF2 in developing rat brains. Conservation and enrichment of these sites are analyzed here for their association with functionality and variability of motifs in genes that have been shown to fall under the control of MEF2 in excitatory neurons.en_US
dc.description.abstract(cont.) The relationships between regulatory motif content, motif functionality, and expression of neuronal genes investigated in this work can help elucidate how programs of gene expression are controlled---and hence how they might go awry-- -in the brain.en_US
dc.description.statementofresponsibilityby David Alan Harmin.en_US
dc.format.extent69 p.en_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.subjectHarvard University--MIT Division of Health Sciences and Technology.en_US
dc.titleGenomic studies of motif enrichment and conservation in the regulation of gene expression in the brainen_US
dc.typeThesisen_US
dc.description.degreeS.M.en_US
dc.contributor.departmentHarvard University--MIT Division of Health Sciences and Technology.en_US
dc.identifier.oclc261571753en_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record