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cis-acting determinants that control...

Yang, Shu Yuan Shyenne.

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cis-acting determinants that control activation induced cytidine deaminase (AID)-mediated sequence diversification.

Record Type:	Electronic resources : Monograph/item
Title/Author:	cis-acting determinants that control activation induced cytidine deaminase (AID)-mediated sequence diversification./
Author:	Yang, Shu Yuan Shyenne.
Description:	123 p.
Notes:	Source: Dissertation Abstracts International, Volume: 67-12, Section: B, page: 6997.
Contained By:	Dissertation Abstracts International67-12B.
Subject:	Biology, Molecular. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3243729
ISBN:	9780542996283

cis-acting determinants that control activation induced cytidine deaminase (AID)-mediated sequence diversification.
Yang, Shu Yuan Shyenne.

cis-acting determinants that control activation induced cytidine deaminase (AID)-mediated sequence diversification. - 123 p.

Source: Dissertation Abstracts International, Volume: 67-12, Section: B, page: 6997.

Thesis (Ph.D.)--Yale University, 2006.

Gene conversion (GCV) and somatic hypermutation (SHM) are two activation induced cytidine deaminase (AID)-dependent processes crucial for diversifying the variable region sequence of rearranged immunoglobulin (Ig) loci of B cells. A key molecular feature of genes capable of undergoing AID-dependent sequence diversification is active transcription, and it has been suggested that high levels of transcription could be sufficient for a region to become a target for AID. We explored this idea by testing the mutability of non-Ig transcription cassettes in Ig and non-Ig loci of the chicken B cell line DT40. We found that such cassettes did not act as stable mutation targets; however, they were mutated in an AID-dependent manner for a limited time post-integration. These results strongly argue that additional mutation targeting mechanisms must operate together with the requirement for transcription. Moreover, newly integrated, highly transcribed DNA has molecular characteristics that render it transiently susceptible to modification by AID, with potential implications for how mis-targeting of AID-dependent processes occurs.

ISBN: 9780542996283Subjects--Topical Terms:

1017719
Biology, Molecular.

cis-acting determinants that control activation induced cytidine deaminase (AID)-mediated sequence diversification.
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035 $a (UMI)AAI3243729
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040 $a UMI $c UMI
100 1 $a Yang, Shu Yuan Shyenne. $3 1917972
245 1 0 $a cis-acting determinants that control activation induced cytidine deaminase (AID)-mediated sequence diversification.
300 $a 123 p.
500 $a Source: Dissertation Abstracts International, Volume: 67-12, Section: B, page: 6997.
500 $a Adviser: David G. Schatz.
502 $a Thesis (Ph.D.)--Yale University, 2006.
520 $a Gene conversion (GCV) and somatic hypermutation (SHM) are two activation induced cytidine deaminase (AID)-dependent processes crucial for diversifying the variable region sequence of rearranged immunoglobulin (Ig) loci of B cells. A key molecular feature of genes capable of undergoing AID-dependent sequence diversification is active transcription, and it has been suggested that high levels of transcription could be sufficient for a region to become a target for AID. We explored this idea by testing the mutability of non-Ig transcription cassettes in Ig and non-Ig loci of the chicken B cell line DT40. We found that such cassettes did not act as stable mutation targets; however, they were mutated in an AID-dependent manner for a limited time post-integration. These results strongly argue that additional mutation targeting mechanisms must operate together with the requirement for transcription. Moreover, newly integrated, highly transcribed DNA has molecular characteristics that render it transiently susceptible to modification by AID, with potential implications for how mis-targeting of AID-dependent processes occurs.
520 $a To investigate the cis-acting elements involved in targeting GCV and SHM specifically to Ig loci, we have analyzed the role of two endogenous Ig elements in GCV/SHM in DT40 cells. Promoter substitution experiments led to identification of a strong RNA polymerase II-driven promoter incapable of supporting efficient GCV/SHM. This surprising finding indicated that high levels of transcription are not sufficient for robust GCV/SHM in Ig loci. In addition, they indicate that contributions of promoters to GCV/SHM extend beyond driving transcription. Deletion of the Ig light chain enhancer in a context in which high-level transcription was not compromised showed that the enhancer is not necessary for GCV/SHM. Our results indicate that cis-acting elements are important for Ig gene diversification, and we propose that targeting specificity is achieved through the combined action of several Ig locus elements that include the promoter.
590 $a School code: 0265.
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Health Sciences, Immunology. $3 1017716
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710 2 0 $a Yale University. $3 515640
773 0 $t Dissertation Abstracts International $g 67-12B.
790 1 0 $a Schatz, David G., $e advisor
790 $a 0265
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3243729