Tandem repeat modification during double-strand break repair induced by an engineered TAL effector nuclease in zebrafish genome.

Tandem repeats (TRs) are abundant and widely distributed in eukaryotic genomes. TRs are thought to have various functions in gene transcription, DNA methylation, nucleosome position and chromatin organization. Variation of repeat units in the genome is observed in association with a number of diseas...

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Main Authors: Wanxu Huang, Jianbo Zheng, Ying He, Chen Luo
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3873399?pdf=render
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author Wanxu Huang
Jianbo Zheng
Ying He
Chen Luo
author_facet Wanxu Huang
Jianbo Zheng
Ying He
Chen Luo
author_sort Wanxu Huang
collection DOAJ
description Tandem repeats (TRs) are abundant and widely distributed in eukaryotic genomes. TRs are thought to have various functions in gene transcription, DNA methylation, nucleosome position and chromatin organization. Variation of repeat units in the genome is observed in association with a number of diseases, such as Fragile X Syndrome, Huntington's disease and Friedreich's ataxia. However, the underlying mechanisms involved are poorly understood, largely owing to the technical limitations in modification of TRs at definite sites in the genome in vivo. Transcription activator-like effector nucleases (TALENs) are widely used in recent years in gene targeting for their specific binding to target sequences when engineered in vitro. Here, we show that the repair of a double-strand break (DSB) induced by TALENs adjacent to a TR can produce serial types of mutations in the TR region. Sequencing analysis revealed that there are three types of mutations induced by the DSB repair, including indels only within the TR region or within the flanking TALEN target region or simutaneously within both regions. Therefore, desired TR mutant types can be conveniently obtained by using engineered TALENs. These results demonstrate that TALENs can serve as a convenient tool for modifying TRs in the genome in studying the functions of TRs.
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spelling doaj.art-920514dce3974fadbf4237b317f9ddab2022-12-21T19:47:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8417610.1371/journal.pone.0084176Tandem repeat modification during double-strand break repair induced by an engineered TAL effector nuclease in zebrafish genome.Wanxu HuangJianbo ZhengYing HeChen LuoTandem repeats (TRs) are abundant and widely distributed in eukaryotic genomes. TRs are thought to have various functions in gene transcription, DNA methylation, nucleosome position and chromatin organization. Variation of repeat units in the genome is observed in association with a number of diseases, such as Fragile X Syndrome, Huntington's disease and Friedreich's ataxia. However, the underlying mechanisms involved are poorly understood, largely owing to the technical limitations in modification of TRs at definite sites in the genome in vivo. Transcription activator-like effector nucleases (TALENs) are widely used in recent years in gene targeting for their specific binding to target sequences when engineered in vitro. Here, we show that the repair of a double-strand break (DSB) induced by TALENs adjacent to a TR can produce serial types of mutations in the TR region. Sequencing analysis revealed that there are three types of mutations induced by the DSB repair, including indels only within the TR region or within the flanking TALEN target region or simutaneously within both regions. Therefore, desired TR mutant types can be conveniently obtained by using engineered TALENs. These results demonstrate that TALENs can serve as a convenient tool for modifying TRs in the genome in studying the functions of TRs.http://europepmc.org/articles/PMC3873399?pdf=render
spellingShingle Wanxu Huang
Jianbo Zheng
Ying He
Chen Luo
Tandem repeat modification during double-strand break repair induced by an engineered TAL effector nuclease in zebrafish genome.
PLoS ONE
title Tandem repeat modification during double-strand break repair induced by an engineered TAL effector nuclease in zebrafish genome.
title_full Tandem repeat modification during double-strand break repair induced by an engineered TAL effector nuclease in zebrafish genome.
title_fullStr Tandem repeat modification during double-strand break repair induced by an engineered TAL effector nuclease in zebrafish genome.
title_full_unstemmed Tandem repeat modification during double-strand break repair induced by an engineered TAL effector nuclease in zebrafish genome.
title_short Tandem repeat modification during double-strand break repair induced by an engineered TAL effector nuclease in zebrafish genome.
title_sort tandem repeat modification during double strand break repair induced by an engineered tal effector nuclease in zebrafish genome
url http://europepmc.org/articles/PMC3873399?pdf=render
work_keys_str_mv AT wanxuhuang tandemrepeatmodificationduringdoublestrandbreakrepairinducedbyanengineeredtaleffectornucleaseinzebrafishgenome
AT jianbozheng tandemrepeatmodificationduringdoublestrandbreakrepairinducedbyanengineeredtaleffectornucleaseinzebrafishgenome
AT yinghe tandemrepeatmodificationduringdoublestrandbreakrepairinducedbyanengineeredtaleffectornucleaseinzebrafishgenome
AT chenluo tandemrepeatmodificationduringdoublestrandbreakrepairinducedbyanengineeredtaleffectornucleaseinzebrafishgenome