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Investigating DNA methylation dynami...

Rosser, James Michael.

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Investigating DNA methylation dynamics with transgenic LINE-1 mouse models.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Investigating DNA methylation dynamics with transgenic LINE-1 mouse models./
Author:	Rosser, James Michael.
Description:	265 p.
Notes:	Source: Dissertation Abstracts International, Volume: 75-02(E), Section: B.
Contained By:	Dissertation Abstracts International75-02B(E).
Subject:	Biology, Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3598115
ISBN:	9781303465895

Investigating DNA methylation dynamics with transgenic LINE-1 mouse models.
Rosser, James Michael.

Investigating DNA methylation dynamics with transgenic LINE-1 mouse models. - 265 p.

Source: Dissertation Abstracts International, Volume: 75-02(E), Section: B.

Thesis (Ph.D.)--Washington State University, 2013.

The mouse and human genomes are saturated with retrotransposons or repetitive elements. While most repetitive elements cannot mobilize by themselves, a specific class of retrotransposon, Long Interspersed Element Type 1 (LINE-1, L1) encodes the molecular machinery to move itself and other retroelements, classifying it as the only autonomous repetitive element found in both genomes. To explore the inner-workings of L1, research groups have developed L1 transgenes capable of indicating retrotransposition through reporter gene expression or molecular markers. However, many L1 transgenes have low activity, hindering progress to better understand L1 biology. A major advancement toward generating a better L1 transgene was made with the construction of a hyperactive L1 transgene (ORFeus) capable of retrotransposing at high levels in mice. In the first study, we further characterized the retrotransposition activity of both a high- and single-copy ORFeus transgene in mice and reported the highest retrotransposition activity in somatic tissues hitherto. The second study used the ORFeus transgene to incorporate poly(A) repeats into the genome through retrotransposition to study their mutability dynamics. We observed dynamic and rapid shortening of long poly(A) repeats (>100 As) which led to somatic and germ cell mosaicism. In the third study, we used the ORFeus transgene to mobilize a CpG-rich sequence to random locations in the mouse genome and characterized the DNA methylation patterns. We observed a striking difference in somatic and germ cell methylation; while insertions in somatic tissues were consistently hypermethylated, insertions in germ cells were hypomethylated. In the fourth study, we examined the flanking genomic regions of the germline insertions for changes in methylation pattern. Here, we observed a two-way cross talk between the methylation state of the insertions and flanking genomic DNA. The work presented here demonstrates how, by using L1 transgenes in an in vivo model, we were able to capture the subtle ways L1 mobilization changes the dynamics of the genome and epigenome.

ISBN: 9781303465895Subjects--Topical Terms:

1017730
Biology, Genetics.

Investigating DNA methylation dynamics with transgenic LINE-1 mouse models.
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100 1 $a Rosser, James Michael. $3 2099964
245 1 0 $a Investigating DNA methylation dynamics with transgenic LINE-1 mouse models.
300 $a 265 p.
500 $a Source: Dissertation Abstracts International, Volume: 75-02(E), Section: B.
500 $a Adviser: Wenfeng An.
502 $a Thesis (Ph.D.)--Washington State University, 2013.
520 $a The mouse and human genomes are saturated with retrotransposons or repetitive elements. While most repetitive elements cannot mobilize by themselves, a specific class of retrotransposon, Long Interspersed Element Type 1 (LINE-1, L1) encodes the molecular machinery to move itself and other retroelements, classifying it as the only autonomous repetitive element found in both genomes. To explore the inner-workings of L1, research groups have developed L1 transgenes capable of indicating retrotransposition through reporter gene expression or molecular markers. However, many L1 transgenes have low activity, hindering progress to better understand L1 biology. A major advancement toward generating a better L1 transgene was made with the construction of a hyperactive L1 transgene (ORFeus) capable of retrotransposing at high levels in mice. In the first study, we further characterized the retrotransposition activity of both a high- and single-copy ORFeus transgene in mice and reported the highest retrotransposition activity in somatic tissues hitherto. The second study used the ORFeus transgene to incorporate poly(A) repeats into the genome through retrotransposition to study their mutability dynamics. We observed dynamic and rapid shortening of long poly(A) repeats (>100 As) which led to somatic and germ cell mosaicism. In the third study, we used the ORFeus transgene to mobilize a CpG-rich sequence to random locations in the mouse genome and characterized the DNA methylation patterns. We observed a striking difference in somatic and germ cell methylation; while insertions in somatic tissues were consistently hypermethylated, insertions in germ cells were hypomethylated. In the fourth study, we examined the flanking genomic regions of the germline insertions for changes in methylation pattern. Here, we observed a two-way cross talk between the methylation state of the insertions and flanking genomic DNA. The work presented here demonstrates how, by using L1 transgenes in an in vivo model, we were able to capture the subtle ways L1 mobilization changes the dynamics of the genome and epigenome.
590 $a School code: 0251.
650 4 $a Biology, Genetics. $3 1017730
690 $a 0369
710 2 $a Washington State University. $b Molecular Biosciences. $3 2099965
773 0 $t Dissertation Abstracts International $g 75-02B(E).
790 $a 0251
791 $a Ph.D.
792 $a 2013
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3598115