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dc.contributor.authorHsiau, Timothy H.-C.
dc.contributor.authorDiaconu, Claudiu
dc.contributor.authorMyers, Connie A.
dc.contributor.authorLee, Jongwoo
dc.contributor.authorCepko, Constance L.
dc.contributor.authorCorbo, Joseph C.
dc.date.accessioned2010-12-08T17:08:24Z
dc.date.issued2007
dc.identifier.citationHsiau, Timothy H.-C., Claudiu Diaconu, Connie A. Myers, Jongwoo Lee, Constance L. Cepko, and Joseph C. Corbo. 2007. The Cis-regulatory logic of the mammalian photoreceptor transcriptional network. PLoS ONE 2(7): e643.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4621008
dc.description.abstractThe photoreceptor cells of the retina are subject to a greater number of genetic diseases than any other cell type in the human body. The majority of more than 120 cloned human blindness genes are highly expressed in photoreceptors. In order to establish an integrative framework in which to understand these diseases, we have undertaken an experimental and computational analysis of the network controlled by the mammalian photoreceptor transcription factors, Crx, Nrl, and Nr2e3. Using microarray and in situ hybridization datasets we have produced a model of this network which contains over 600 genes, including numerous retinal disease loci as well as previously uncharacterized photoreceptor transcription factors. To elucidate the connectivity of this network, we devised a computational algorithm to identify the photoreceptor-specific cis-regulatory elements (CREs) mediating the interactions between these transcription factors and their target genes. In vivo validation of our computational predictions resulted in the discovery of 19 novel photoreceptor-specific CREs near retinal disease genes. Examination of these CREs permitted the definition of a simple cis-regulatory grammar rule associated with high-level expression. To test the generality of this rule, we used an expanded form of it as a selection filter to evolve photoreceptor CREs from random DNA sequences in silico. When fused to fluorescent reporters, these evolved CREs drove strong, photoreceptor-specific expression in vivo. This study represents the first systematic identification and in vivo validation of CREs in a mammalian neuronal cell type and lays the groundwork for a systems biology of photoreceptor transcriptional regulation.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0000643en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1916400/pdf/en_US
dash.licenseLAA
dc.subjectcell biologyen_US
dc.subjectcomputational biologyen_US
dc.subjectdevelopmental biologyen_US
dc.subjectgenetics and genomicsen_US
dc.subjectneuroscienceen_US
dc.titleThe Cis-regulatory Logic of the Mammalian Photoreceptor Transcriptional Networken_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorCepko, Constance L.
dc.date.available2010-12-08T17:08:24Z
dash.affiliation.otherHMS^Ophthalmologyen_US
dash.affiliation.otherHMS^Geneticsen_US
dc.identifier.doi10.1371/journal.pone.0000643*
dash.contributor.affiliatedCepko, Constance


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