Identification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance

被引：96

作者：

Kazachenka, Anastasiya ^{[1
]}

Bertozzi, Tessa M. ^{[1
]}

Sjoberg-Herrera, Marcela K. ^{[2
,3
]}

Walker, Nic ^{[1
,4
]}

Gardner, Joseph ^{[1
]}

Gunning, Richard ^{[2
]}

Pahita, Elena ^{[1
]}

Adams, Sarah ^{[1
]}

Adams, David

Ferguson-Smith, Anne C. ^{[1
]}

机构：

[1] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England

[2] Wellcome Trust Sanger Inst, Expt Canc Genet, Cambridge CB10 1SA, England

[3] Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Biol Celular & Mol, Santiago, Chile

[4] Cambridge Epigenetix, Trinity Bldg,Chesterford Business Pk, Saffron Walden CB10 1XL, Essex, England

来源：

CELL | 2018年 / 175卷 / 05期

基金：

英国医学研究理事会; 英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

TRANSGENERATIONAL INHERITANCE; ENDOGENOUS RETROVIRUSES; DIFFERENTIAL EXPRESSION; EPIGENETIC INHERITANCE; GENE-EXPRESSION; SEQUENCE; METHYLATION; GENOME; TRANSCRIPTION; MUTATIONS;

D O I：

10.1016/j.cell.2018.09.043

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Generally repressed by epigenetic mechanisms, retrotransposc represent around 40% of the murine genome. At the Agouti viable yellow (A(vy)) 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 A(vy) 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 reconstruct. in of metastable epigenetic states and challenging the generalizability of non-genetic inheritance at these regions.

引用

页码：1259 / +

页数：26

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