Show simple item record

dc.contributor.advisorSemple, Colinen
dc.contributor.advisorAitken, Stuarten
dc.contributor.authorVacca, Annalauraen
dc.date.accessioned2020-02-10T11:32:06Z
dc.date.available2020-02-10T11:32:06Z
dc.date.issued2019-12-06
dc.identifier.urihttps://hdl.handle.net/1842/36761
dc.identifier.urihttp://dx.doi.org/10.7488/era/66
dc.description.abstractThe promoters of immediate early genes (IEGs) are rapidly activated in response to an external stimulus. These genes, also known as primary response genes, have been identified in a range of cell types, under diverse extracellular signals and using varying experimental protocols. Genomic dissection on a case-by-case basis has not resulted in a comprehensive catalogue of IEGs. I completed a rigorous meta-analysis of eight genome-wide FANTOM5 CAGE (cap analysis of gene expression) time-course datasets, and it revealed successive waves of promoter activation in IEGs, recapitulating known relationships between cell types and stimuli. I found a set of 57 (42 protein-coding) candidate IEGs possessing promoters that consistently drive a rapid but transient increase in expression following external stimulation. These genes show significant enrichment for known IEGs reported previously, pathways associated with the immediate early response, and include a number of non-coding RNAs with roles in proliferation and differentiation. There was strong conservation of the ordering of activation for these genes, such that 77 pairwise promoter activation orderings were conserved. Leveraging comprehensive CAGE time series data across cell types, I also observed extensive alternative promoter usage by such genes, which is likely to hinder their discovery from previous, smaller-scale studies. The common activation ordering of the core set of early-responding genes I identified may indicate conserved underlying regulatory mechanisms. By contrast, the considerably larger number of transiently activated genes that are specific to each cell type and stimulus illustrates the breadth of the primary response.en
dc.language.isoen
dc.publisherThe University of Edinburghen
dc.relation.hasversionVacca, A., et al. (2018). “Conserved temporal ordering of promoter activation implicates common mechanisms governing the immediate early response across cell types and stimuli.” Open biology, 8(8), 180011.en
dc.subjectimmediate-early genesen
dc.subjectIEGsen
dc.subjectFANTOM5 projecten
dc.subjectXBP1en
dc.titleConserved temporal ordering of promoter activation implicates common mechanisms governing the immediate early response across cell types and stimulien
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


Files in this item

This item appears in the following Collection(s)

Show simple item record