SRA-domain proteins required for DRM2-mediated de novo DNA methylation.

SRA-domain proteins required for DRM2-mediated de novo DNA methylation.
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DOI:
10.1371/journal.pgen.1000280
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发表时间:
2008-11
期刊:
影响因子:
4.5
通讯作者:
Jacobsen SE
Jacobsen SE
中科院分区:
生物学2区
文献类型:
--
作者:
Johnson LM;Law JA;Khattar A;Henderson IR;Jacobsen SE

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从头DNA甲基化和DNA甲基化在不对称序列环境中的维持由植物(DRM 2)和动物(DNMT 3a/B)中的同源蛋白催化。在植物中,DRM 2的靶向依赖于小干扰RNA(siRNA),尽管分子细节仍不清楚。在这里,我们表明,两个SRA结构域蛋白(SUVH 9和SUVH 2)也是至关重要的DRM 2介导的从头和维持DNA甲基化拟南芥。在一些基因座,SUV H9和SUV H2冗余地起作用,而在其他基因座,仅需要SUV H2,并且该基因座特异性与SUV H9和SUV H2内的SRA结构域的不同DNA结合亲和力相关。具体而言,SUV H9优先结合甲基化的不对称位点,而SUV H2优先结合甲基化的CG位点。suvh 9和suvh 2突变不会消除siRNA,表明SUVH 9和SUVH 2在RNA指导的DNA甲基化途径中的作用。有了这些新的结果,很明显,SRA结构域蛋白参与了拟南芥中导致DNA甲基化的三条途径中的每一条。我们的基因遗传在决定我们是谁和我们拥有的特征方面起着重要作用。然而,在过去的十年里,人们越来越清楚地认识到,除了我们继承的基因之外,第二层次的信息对这些基因的表达至关重要。这些信息以DNA(DNA甲基化)或包装DNA的蛋白质(组蛋白)的修饰形式出现。这些修饰可以决定基因是表达还是沉默。在本文中,我们确定了两个新的基因,是一个DNA甲基化靶向途径的一部分,在模式植物A。thaliana.这两个密切相关的基因的破坏阻止了细胞DNA甲基转移酶之一的DNA甲基化。然而,这些基因不仅仅是多余的。它们都能够结合甲基化的DNA,但它们对基因组中特定序列的偏好不同。这种与甲基化DNA结合的能力表明这些蛋白质有助于靶向或保留基因组特定区域的修饰装置。这些结果很重要,因为它们确定了这一重要细胞过程中的两个新参与者,并使我们更接近于理解表观遗传修饰如何靶向特定基因。
De novo DNA methylation and the maintenance of DNA methylation in asymmetrical sequence contexts is catalyzed by homologous proteins in plants (DRM2) and animals (DNMT3a/b). In plants, targeting of DRM2 depends on small interfering RNAs (siRNAs), although the molecular details are still unclear. Here, we show that two SRA-domain proteins (SUVH9 and SUVH2) are also essential for DRM2-mediated de novo and maintenance DNA methylation in Arabidopsis thaliana. At some loci, SUVH9 and SUVH2 act redundantly, while at other loci only SUVH2 is required, and this locus specificity correlates with the differing DNA-binding affinity of the SRA domains within SUVH9 and SUVH2. Specifically, SUVH9 preferentially binds methylated asymmetric sites, while SUVH2 preferentially binds methylated CG sites. The suvh9 and suvh2 mutations do not eliminate siRNAs, suggesting a role for SUVH9 and SUVH2 late in the RNA-directed DNA methylation pathway. With these new results, it is clear that SRA-domain proteins are involved in each of the three pathways leading to DNA methylation in Arabidopsis. Our genetic heritage plays an important role in determining who we are and the characteristics we possess. However, in the past decade it has become increasingly clear that in addition to the genes we inherit, a second level of information is critical for expression of these genes. This information takes the form of modifications to either the DNA (DNA methylation) or the proteins that package the DNA (histones). These modifications can determine whether a gene is expressed or silenced. In this paper, we identify two new genes that are part of a DNA methylation–targeting pathway in the model plant A. thaliana. Disruption of these two closely related genes prevents DNA methylation by one of the cellular DNA methyltransferases. However, these genes are not simply redundant. They are both capable of binding methylated DNA, but differ in their preference for specific sequences in the genome. This ability to bind to methylated DNA suggests that these proteins help target or retain the modification apparatus at particular regions of the genome. These results are important in that they identify two new players in this vital cellular process and bring us closer to understanding how epigenetic modifications can be targeted to specific genes.
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