Access to DNA establishes a secondary target site bias for the yeast retrotransposon Ty5
Access to DNA establishes a secondary target site bias for the yeast retrotransposon Ty5
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DOI：
10.1073/pnas.1103665108
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发表时间：
2011-12-20
影响因子：
11.1
通讯作者：
Voytas, Daniel F.
中科院分区：
文献类型：
--
作者：
Baller, Joshua A.;Gao, Jiquan;Voytas, Daniel F.
许多逆转录转座子和逆转录病毒的整合位点由逆转录元件编码的整合酶和特异性DNA结合蛋白之间的相互作用决定。由于Ty5整合酶与异染色质蛋白沉默信息调节因子4之间的相互作用，酵母属反转录转座子Ty5优先整合到异染色质中。我们将超过14，000个Ty5插入定位到S.酿酒酵母基因组中，其中76%发生在异染色质中，这与Ty5的已知靶位点偏倚一致。使用逻辑回归，评估Ty5插入与各种染色体特征（例如核小体的全基因组分布和组蛋白修饰）之间的关联。Ty5插入位点，无论它们是否发生在异染色质或常染色质中，都与DNA酶超敏感的、无核小体的侧翼基因区域密切相关。我们的数据支持一个模型，其中沉默信息调节因子4将Ty5整合机制拴系到异染色质的结构域，然后基于DNA访问选择特定的靶位点，导致次级靶位点偏倚。对于常染色质中的插入，DNA接近是靶位点选择的主要决定因素。Ty5的次要靶位点偏好的一个结果是编码序列中的插入很少发生，这可以保持基因组完整性。
Integration sites for many retrotransposons and retroviruses are determined by interactions between retroelement-encoded integrases and specific DNA-bound proteins. The Saccharomyces retrotransposon Ty5 preferentially integrates into heterochromatin because of interactions between Ty5 integrase and the heterochromatin protein silent information regulator 4. We mapped over 14,000 Ty5 insertions onto the S. cerevisiae genome, 76% of which occurred in heterochromatin, which is consistent with the known target site bias of Ty5. Using logistic regression, associations were assessed between Ty5 insertions and various chromosomal features such as genome-wide distributions of nucleosomes and histone modifications. Sites of Ty5 insertion, regardless of whether they occurred in heterochromatin or euchromatin, were strongly associated with DNase hypersensitive, nucleosome-free regions flanking genes. Our data support a model wherein silent information regulator 4 tethers the Ty5 integration machinery to domains of heterochromatin, and then, specific target sites are selected based on DNA access, resulting in a secondary target site bias. For insertions in euchromatin, DNA access is the primary determinant of target site choice. One consequence of the secondary target site bias of Ty5 is that insertions in coding sequences occur infrequently, which may preserve genome integrity.