| Type of Document |
Dissertation |
| Author |
Oestreich, Kenneth Joseph
|
| Author's Email Address |
ken.oestreich@vanderbilt.edu |
| URN |
etd-07142006-113440 |
| Title |
REGULATION OF T CELL RECEPTOR GENE ASSEMBLY BY LOCAL AND LONG-RANGE CHANGES IN CHROMATIN ACCESSIBILITY |
| Degree |
PhD |
| Department |
Microbiology and Immunology |
| Advisory Committee |
| Advisor Name |
Title |
| Wasif Khan |
Committee Chair |
| Ellen Fanning |
Committee Member |
| Eugene Oltz |
Committee Member |
| James W. Thomas |
Committee Member |
| Roger Chalkley |
Committee Member |
| Stephen Brandt |
Committee Member |
|
| Keywords |
- T Cell Receptor
- Cis-acting elements
- Chromatin Structure
|
| Date of Defense |
2006-07-07 |
| Availability |
unrestricted |
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.
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| Files |
| Filename |
Size |
Approximate Download Time
(Hours:Minutes:Seconds)
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| 28.8 Modem |
56K Modem |
ISDN (64 Kb) |
ISDN (128 Kb) |
Higher-speed Access |
| |
Dissertation.pdf |
1.57 Mb |
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