dc.creator | Oestreich, Kenneth Joseph | |
dc.date.accessioned | 2020-08-22T17:24:05Z | |
dc.date.available | 2007-07-19 | |
dc.date.issued | 2006-07-19 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-07142006-113440 | |
dc.identifier.uri | http://hdl.handle.net/1803/12981 | |
dc.description.abstract | Antigen receptor gene assembly is governed by transcriptional promoters and enhancers that communicate over large distances and modulate chromatin accessibility to V(D)J recombinase. The precise role of these cis-acting elements in opening chromatin at recombinase targets and the mechanisms underlying their collaboration remain unclear. I show that the TCR beta enhancer (Ebeta) directs long-range chromatin opening over both DbetaJbeta clusters. Strikingly, chromatin associated with the Dbeta1 gene segment is refractory to Ebeta-mediated opening. Accessibility at Dbeta1 is accompanied by the formation of a stable holocomplex between a Dbeta-proximal promoter, PDbeta1, and Ebeta. These findings indicate a stepwise process for DbetaJbeta recombination that relies on distinct aspects of Ebeta activity: an intrinsic function that directs general chromatin opening and a cooperative function with PDbeta1 that facilitates the unmasking of the Dbeta1 gene segment, triggering TCR beta gene assembly. | |
dc.format.mimetype | application/pdf | |
dc.subject | Chromatin Structure | |
dc.subject | Cis-acting elements | |
dc.subject | T Cell Receptor | |
dc.title | Regulation of T cell receptor gene assembly by local and long-range changes in chromatin accessibility | |
dc.type | dissertation | |
dc.contributor.committeeMember | Stephen Brandt | |
dc.contributor.committeeMember | James W. Thomas | |
dc.contributor.committeeMember | Ellen Fanning | |
dc.contributor.committeeMember | Roger Chalkley | |
dc.contributor.committeeMember | Eugene Oltz | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Microbiology and Immunology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2007-07-19 | |
local.embargo.lift | 2007-07-19 | |
dc.contributor.committeeChair | Wasif Khan | |