Identification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance.
Identification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance.
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DOI：
10.1016/j.cell.2018.09.043
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发表时间：
2018-11-15
期刊：
影响因子：
64.5
通讯作者：
Ferguson-Smith AC
中科院分区：
文献类型：
--
作者：
Kazachenka A;Bertozzi TM;Sjoberg-Herrera MK;Walker N;Gardner J;Gunning R;Pahita E;Adams S;Adams D;Ferguson-Smith AC
逆转录转座子通常受到表观遗传机制的抑制，约占小鼠基因组的40%。在Agouti活黄色（Avy）位点，内源性A颗粒（IAP）类逆转录病毒（ERV）逆转录到Agouti衣色位点上游，提供了一个在遗传相同个体中可变DNA甲基化的替代启动子。这就导致了被毛颜色的可变表达性，这是跨代遗传的。在这里，系统的全基因组筛选鉴定出多种具有Avy表观遗传特性的C57BL/6J小鼠iap。每种甲基化在个体内表现出稳定的甲基化状态，但在个体之间有所不同。只有在极少数情况下，它们才会作为启动子控制邻近基因的表达。它们的甲基化状态在个体中具有位点特异性，并且它们的侧翼区域富含CTCF。可变甲基化的IAPs在受精后被重新编程，并在下一代中作为可变位点重新建立，这表明亚稳态表观遗传状态的重建，并挑战了这些区域非遗传遗传的普遍性。在近交系小鼠VM-IAPs中定义的可变甲基化重复元件库两侧是CTCF结合位点，很少作为启动子甲基化变异性从一代到下一代被重新建立，亲本甲基化状态的记忆是一个例外，而不是规则。对可变甲基化内源性逆转录病毒的全基因组调查显示，受精后甲基化状态的重编程是常见的。挑战这些位点的跨代非基因遗传范式。
Generally repressed by epigenetic mechanisms, retrotransposons represent around 40% of the murine genome. At the Agouti viable yellow (Avy) locus, an endogenous retrovirus (ERV) of the intracisternal A particle (IAP) class retrotransposed upstream of the agouti coat-color locus, providing an alternative promoter that is variably DNA methylated in genetically identical individuals. This results in variable expressivity of coat color that is inherited transgenerationally. Here, a systematic genome-wide screen identifies multiple C57BL/6J murine IAPs with Avy epigenetic properties. Each exhibits a stable methylation state within an individual but varies between individuals. Only in rare instances do they act as promoters controlling adjacent gene expression. Their methylation state is locus-specific within an individual, and their flanking regions are enriched for CTCF. Variably methylated IAPs are reprogrammed after fertilization and re-established as variable loci in the next generation, indicating reconstruction of metastable epigenetic states and challenging the generalizability of non-genetic inheritance at these regions. Repertoire of variably methylated repeat elements defined in inbred mice VM-IAPs are flanked by CTCF binding sites, and very few act as promoters Methylation variability is re-established from one generation to the next Memory of parental methylation state is an exception rather than the rule A genome-wide interrogation of variably methylated endogenous retroviruses shows common reprogramming of methylation states after fertilization, challenging the paradigm of transgenerational non-genetic inheritance at such loci.
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影响因子：
4.5
作者：
Kobayashi H;Sakurai T;Imai M;Takahashi N;Fukuda A;Yayoi O;Sato S;Nakabayashi K;Hata K;Sotomaru Y;Suzuki Y;Kono T
通讯作者：
Kono T
影响因子：
3.1
作者：
DICKIES, MM
通讯作者：
DICKIES, MM
影响因子：
12.3
作者：
Daxinger L;Harten SK;Oey H;Epp T;Isbel L;Huang E;Whitelaw N;Apedaile A;Sorolla A;Yong J;Bharti V;Sutton J;Ashe A;Pang Z;Wallace N;Gerhardt DJ;Blewitt ME;Jeddeloh JA;Whitelaw E
通讯作者：
Whitelaw E
在小鼠表观遗传敏感等位基因上DNA甲基化的动态重编程。
影响因子：
4.5
作者：
Blewitt ME;Vickaryous NK;Paldi A;Koseki H;Whitelaw E
通讯作者：
Whitelaw E
影响因子：
4.4
作者：
Faulk, Christopher;Barks, Amanda;Dolinoy, Dana C.
通讯作者：
Dolinoy, Dana C.