Germline-derived DNA methylation and early embryo epigenetic reprogramming: The selected survival of imprints

Monk, David

doi:10.1016/j.biocel.2015.04.014

Cited by 85 publications

(58 citation statements)

References 116 publications

(133 reference statements)

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“…The collective multilineage manifestations of TGCTs, taken together with core hypo-and hypermethylation modules and somatic subtype-dependent methylation, is consistent with antecedent physiologic global erasure in a PGC ancestor, followed by acquisition of mCpH-pluri and the malignancyassociated core hypermethylation module en route to ECs and, finally, establishment of differentiated derivative-specific methylation, the final two steps analogous to that of embryonic somatic de novo methylation (for review, see Monk 2015). The strong coexpression of DNMT3B and mCpH-pluri in both ECs and benign pluripotent states further supports the model whereby mCpHpluri is established de novo, and then upon differentiation to YST and TE, its maintenance is neglected by the more CpG-philic DNMT1 maintenance methyltransferase (Sperger et al 2003;Almstrup et al 2005;Biermann et al 2007;Chedin 2011;Tiedemann et al 2014).…”

Section: Wwwgenomeorgmentioning

confidence: 76%

Imprints and DPPA3 are bypassed during pluripotency- and differentiation-coupled methylation reprogramming in testicular germ cell tumors

et al. 2016

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Testicular germ cell tumors (TGCTs) share germline ancestry but diverge phenotypically and clinically as seminoma (SE) and nonseminoma (NSE), the latter including the pluripotent embryonal carcinoma (EC) and its differentiated derivatives, teratoma (TE), yolk sac tumor (YST), and choriocarcinoma. Epigenomes from TGCTs may illuminate reprogramming in both normal development and testicular tumorigenesis. Herein we investigate pure-histological forms of 130 TGCTs for conserved and subtype-specific DNA methylation, including analysis of relatedness to pluripotent stem cell (ESC, iPSC), primordial germ cell (PGC), and differentiated somatic references. Most generally, TGCTs conserve PGC-lineage erasure of maternal and paternal genomic imprints and DPPA3 (also known as STELLA); however, like ESCs, TGCTs show focal recurrent imprinted domain hypermethylation. In this setting of shared physiologic erasure, NSEs harbor a malignancy-associated hypermethylation core, akin to that of a diverse cancer compendium. Beyond these concordances, we found subtype epigenetic homology with pluripotent versus differentiated states. ECs demonstrate a striking convergence of both CpG and CpH (non-CpG) methylation with pluripotent states; the pluripotential methyl-CpH signature crosses species boundaries and is distinct from neuronal methyl-CpH. EC differentiation to TE and YST entails reprogramming toward the somatic state, with loss of methyl-CpH but de novo methylation of pluripotency loci such as NANOG. Extreme methyl-depletion among SE reflects the PGC methylation nadir. Adjacent to TGCTs, benign testis methylation profiles are determined by spermatogenetic proficiency measured by Johnsen score. In sum, TGCTs share collective entrapment in a PGC-like state of genomic-imprint and DPPA3 erasure, recurrent hypermethylation of cancer-associated targets, and subtype-dependent pluripotent, germline, or somatic methylation.

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Section: Wwwgenomeorgmentioning

confidence: 76%

Imprints and DPPA3 are bypassed during pluripotency- and differentiation-coupled methylation reprogramming in testicular germ cell tumors

et al. 2016

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“…The correct establishment of DNA methylation is essential for the successful development of the embryo following fertilization, primarily due to the necessity for epigenetic marking of genomic imprints (Monk 2015). Following the widespread epigenetic erasure that occurs in the primordial germ cells, oocytes acquire a unique methylation landscape compared to somatic cells (Smallwood et al 2011, Kobayashi et al 2012, SanchezDelgado et al 2016.…”

Section: Methylation Acquisition In the Oocytementioning

confidence: 99%

“…Genomic imprinting refers to the epigenetic mechanism that results in the parent-of-origin monoallelic expression of autosomal genes (Monk 2015). It is a particularly unique epigenetic mechanism, since an individual somatic cell has both active and repressed alleles of the same gene.…”

Section: Genomic Imprintingmentioning

confidence: 99%

NLRPs, the subcortical maternal complex and genomic imprinting

Monk¹,

Sánchez-Delgado²,

Fisher³

2017

Reproduction

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Before activation of the embryonic genome, the oocyte provides many of the RNAs and proteins required for the epigenetic reprogramming and the transition to a totipotent state. Targeted disruption of a subset of oocyte-derived transcripts in mice results in early embryonic lethality and cleavage-stage embryonic arrest as highlighted by the members of the subcortical maternal complex (SCMC). Maternal-effect recessive mutations of NLRP7, KHDC3L and NLRP5 in humans are associated with variable reproductive outcomes, biparental hydatidiform moles (BiHM) and widespread multi-locus imprinting disturbances. The precise mechanism of action of these genes is unknown, but the maternal-effect phenomenon suggests a function during early pre-implantation development, while biochemical and genetic studies implement them as SCMC members or interacting partners. In this review article, we discuss the role of the NLRP family members and the SCMC proteins in the establishment of genomic imprints and post-zygotic methylation maintenance, the recent advances made in the understanding of the biology involved in BiHM formation and the wider roles of the SCMC in mammalian reproduction.Reproduction (2017) 154 R161-R170

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“…Although few human studies have been conducted on this subject, existing studies support the possibility of epigenetic inheritance through the human paternal germ line. The human studies have shown that epigenetic changes in spermatozoa can occur rapidly and in response to different nutritional statuses or other lifestyle conditions (Hoyo et al 2012, Soubry et al 2013, 2015. These studies have not yet provided an in-depth understanding of the specific mechanisms behind epigenetic inheritance or exact effect size for the disease risk in offspring.…”

Section: Perspectivesmentioning

confidence: 99%

“…Although genomic remethylation will not be further addressed in this review, the existence of protection against methylation for imprinting DMRs, which specify maternal imprinting on the paternal genome of the embryo should be noted (Fig. 3) (for review Monk 2015). Moreover, gestational exposures potentially affect both the demethylation and remethylation processes, leaving room for epigenetic inheritance through this fourth window of susceptibility.…”

Section: Journal Of Molecular Endocrinologymentioning

confidence: 99%

DNA methylation in epigenetic inheritance of metabolic diseases through the male germ line

Illum

Bak

Lund

et al. 2018

Journal of Molecular Endocrinology

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The global rise in metabolic diseases can be attributed to a complex interplay between biology, behavior and environmental factors. This article reviews the current literature concerning DNA methylation-based epigenetic inheritance (intergenerational and transgenerational) of metabolic diseases through the male germ line. Included are a presentation of the basic principles for DNA methylation in developmental programming, and a description of windows of susceptibility for the inheritance of environmentally induced aberrations in DNA methylation and their associated metabolic disease phenotypes. To this end, escapees, genomic regions with the intrinsic potential to transmit acquired paternal epigenetic information across generations by escaping the extensive programmed DNA demethylation that occurs during gametogenesis and in the zygote, are described. The ongoing descriptive and functional examinations of DNA methylation in the relevant biological samples, in conjugation with analyses of noncoding RNA and histone modifications, hold promise for improved delineation of the effect size and mechanistic background for epigenetic inheritance of metabolic diseases.

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Germline-derived DNA methylation and early embryo epigenetic reprogramming: The selected survival of imprints

Cited by 85 publications

References 116 publications

Imprints and DPPA3 are bypassed during pluripotency- and differentiation-coupled methylation reprogramming in testicular germ cell tumors

Imprints and DPPA3 are bypassed during pluripotency- and differentiation-coupled methylation reprogramming in testicular germ cell tumors

NLRPs, the subcortical maternal complex and genomic imprinting

DNA methylation in epigenetic inheritance of metabolic diseases through the male germ line

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