Depositing centromere repeats induces heritable intragenic heterochromatin establishment and spreading in Arabidopsis.
Depositing centromere repeats induces heritable intragenic heterochromatin establishment and spreading in Arabidopsis.
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DOI：
10.1093/nar/gkad306
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发表时间：
2023-07-07
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
--
作者：
非dna序列表观遗传信息的稳定传递有助于遗传表型变异，从而促进生物多样性。虽然对自发的自然表观基因组变异的研究已经揭示了外显等位基因与植物和动物的广泛生物学性状的关联，但对外显等位基因在基因座特异性方式下的功能、传递机制和稳定性的研究仍然很少。在这里，我们发明了一种DNA序列沉积策略，通过将CEN180卫星重复序列沉积到拟南芥的一个共色靶座中来产生一个位点特异性的外等位基因。利用CRISPR/ cas9介导的敲入系统，我们证明了沉积CEN180重复序列可以诱导异染色质成核，并伴有DNA甲基化、H3K9me2和插入位点核小体占用的变化。有趣的是，DNA甲基化和H3K9me2都被限制在沉积位点内，H3K9me2去甲基化酶IBM1的耗尽使外异染色质繁殖到邻近区域，导致可遗传的靶基因沉默持续至少五代。总之，这些结果证明了使用顺式工程系统创建稳定和位点特异性表观等位基因的前景，并为功能表观基因组研究和位点特异性跨代表观遗传提供了重要见解。着丝粒重复沉积诱导异染色质成核、维持和扩散。
Stable transmission of non-DNA-sequence-based epigenetic information contributes to heritable phenotypic variants and thus to biological diversity. While studies on spontaneous natural epigenome variants have revealed an association of epialleles with a wide range of biological traits in both plants and animals, the function, transmission mechanism, and stability of an epiallele over generations in a locus-specific manner remain poorly investigated. Here, we invented a DNA sequence deposition strategy to generate a locus-specific epiallele by depositing CEN180 satellite repeats into a euchromatic target locus in Arabidopsis. Using CRISPR/Cas9-mediated knock-in system, we demonstrated that depositing CEN180 repeats can induce heterochromatin nucleation accompanied by DNA methylation, H3K9me2, and changes in the nucleosome occupancy at the insertion sites. Interestingly, both DNA methylation and H3K9me2 are restricted within the depositing sites and depletion of an H3K9me2 demethylase IBM1 enables the outward heterochromatin propagation into the neighboring regions, leading to inheritable target gene silencing to persist for at least five generations. Together, these results demonstrate the promise of employing a cis-engineering system for the creation of stable and site-specific epialleles and provide important insights into functional epigenome studies and locus-specific transgenerational epigenetic inheritance. Centromere repeat deposition-induced heterochromatin nucleation, maintenance, and spreading.
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DOI：
10.1073/pnas.2125016118
发表时间：
2021-06-08
影响因子：
11.1
作者：
Ghoshal B;Picard CL;Vong B;Feng S;Jacobsen SE
通讯作者：
Jacobsen SE
DOI：
10.1038/nrm4043
发表时间：
2015-09
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Du J;Johnson LM;Jacobsen SE;Patel DJ
通讯作者：
Patel DJ
影响因子：
13.6
作者：
Crisp PA;Ganguly D;Eichten SR;Borevitz JO;Pogson BJ
通讯作者：
Pogson BJ
DOI：
10.1073/pnas.1716945115
发表时间：
2018-02-27
影响因子：
11.1
作者：
Gallego-Bartolomé J;Gardiner J;Liu W;Papikian A;Ghoshal B;Kuo HY;Zhao JM;Segal DJ;Jacobsen SE
通讯作者：
Jacobsen SE
影响因子：
30.8
作者：
Ciabrelli F;Comoglio F;Fellous S;Bonev B;Ninova M;Szabo Q;Xuéreb A;Klopp C;Aravin A;Paro R;Bantignies F;Cavalli G
通讯作者：
Cavalli G