Refurbishing the germline epigenome: Out with the old, in with the new

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• 作者：Kirsten Hogg^a ; ^b ; Patrick S. Western^a ; ^b ; ^{patrick.western@hudson.au.org" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AID ; activation induced deaminase ; BER ; base excision repair ; CGI ; CpG island ; DNMT ; DNA methyltransferase ; EED ; embryonic ectoderm development ; ERV ; endogenous retrovirus ; EZH ; enhancer of zeste ; GV ; germinal vesicle ; HDAC ; histone deacetylase ; IAP ; intracisternal A-particle ; LTR ; long terminal repeat ; PGCs ; primordial germ cells ; PRC ; polycomb repressive complex ; REs ; repetitive elements ; RNF ; ring finger protein ; TET ; ten-eleven translocation ; TDG ; thymidine ; DNA ; glycosylase ; 5-mC ; 5-methylc
• 刊名：Seminars in Cell & Developmental Biology
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：45
• 期：Complete
• 页码：104-113
• 全文大小：1591 K

文摘

Mammalian germline reprogramming involves the erasure and re-establishment of epigenetic information critical for germ cell function and inheritance in offspring. The bi-faceted nature of such reprogramming ensures germline repression of somatic programmes and the establishment of a carefully constructed epigenome essential for fertilisation and embryonic development in the next generation. While the majority of the germline epigenome is erased in preparation for embryonic development, certain genomic sequences remain resistant to this and may represent routes for transmission of epigenetic changes through the germline. Epigenetic reprogramming is regulated by highly conserved epigenetic modifiers, which function to establish, maintain and remove DNA methylation and chromatin modifications. In this review, we discuss recent findings from a considerable body of work illustrating the critical requirement of epigenetic modifiers that influence the epigenetic signature present in mature gametes, and have the potential to affect developmental outcomes in the offspring. We also briefly discuss the similarities of these mechanisms in the human germline and consider the potential for inheritance of epigenetically induced germline genetic errors that could impact on offspring phenotypes.