scholarly journals Epigenetic marking and repression of porcine endogenous retroviruses

2013 ◽  
Vol 94 (5) ◽  
pp. 960-970 ◽  
Author(s):  
Gernot Wolf ◽  
Anders Lade Nielsen ◽  
Jacob Giehm Mikkelsen ◽  
Finn Skou Pedersen
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Germ Line ◽  
Mammalian Species ◽  
Histone Deacetylation ◽  
Endogenous Retroviruses ◽  
Primer Binding Site ◽  
Retroviral Transduction ◽  
Embryonic Germ Cells ◽  
Epigenetic Repression

Endogenous retroviruses (ERVs) are remnants of retroviral germ line infections and have been identified in all mammals investigated so far. Although the majority of ERVs are degenerated, some mammalian species, such as mice and pigs, carry replication-competent ERVs capable of forming infectious viral particles. In mice, ERVs are silenced by DNA methylation and histone modifications and some exogenous retroviruses were shown to be transcriptionally repressed after integration by a primer-binding site (PBS) targeting mechanism. However, epigenetic repression of porcine ERVs (PERVs) has remained largely unexplored so far. In this study, we screened the pig genome for PERVs using LTRharvest, a tool for de novo detection of ERVs, and investigated various aspects of epigenetic repression of three unrelated PERV families. We found that these PERV families are differentially up- or downregulated upon chemical inhibition of DNA methylation and histone deacetylation in cultured porcine cells. Furthermore, chromatin immunoprecipitation analysis revealed repressive histone methylation marks at PERV loci in primary porcine embryonic germ cells and immortalized embryonic kidney cells. PERV elements belonging to the PERV-γ1 family, which is the only known PERV family that has remained active up to the present, were marked by significantly higher levels of histone methylations than PERV-γ2 and PERV-β3 proviruses. Finally, we tested three PERV-associated PBS sequences for repression activity in murine and porcine cells using retroviral transduction experiments and showed that none of these PBS sequences induced immediate transcriptional silencing in the tested primary porcine cells.

scholarly journals De Novo DNA Methylation in the Male Germ Line Occurs by Default but Is Excluded at Sites of H3K4 Methylation

Cell Reports ◽  
2013 ◽  
Vol 4 (1) ◽  
pp. 205-219 ◽  
Author(s):  
Purnima Singh ◽  
Arthur X. Li ◽  
Diana A. Tran ◽  
Nathan Oates ◽  
Eun-Rim Kang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Germ Line ◽  
H3k4 Methylation ◽  
Male Germ Line

scholarly journals Human Endogenous Retrovirus Family HERV-K(HML-5): Status, Evolution, and Reconstruction of an Ancient Betaretrovirus in the Human Genome

2004 ◽  
Vol 78 (16) ◽  
pp. 8788-8798 ◽  
Author(s):  
Laurence Lavie ◽  
Patrik Medstrand ◽  
Werner Schempp ◽  
Eckart Meese ◽  
Jens Mayer
Keyword(s):  
Human Genome ◽  
Germ Line ◽  
Consensus Sequence ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Open Reading Frames ◽  
Primer Binding Site ◽  
Human Endogenous Retrovirus ◽  
New World Primates ◽  
Human Endogenous Retroviruses

ABSTRACT The human genome harbors numerous distinct families of so-called human endogenous retroviruses (HERV) which are remnants of exogenous retroviruses that entered the germ line millions of years ago. We describe here the hitherto little-characterized betaretrovirus HERV-K(HML-5) family (named HERVK22 in Repbase) in greater detail. Out of 139 proviruses, only a few loci represent full-length proviruses, and many lack gag protease and/or env gene regions. We generated a consensus sequence from multiple alignment of 62 HML-5 loci that displays open reading frames for the four major retroviral proteins. Four HML-5 long terminal repeat (LTR) subfamilies were identified that are associated with monophyletic proviral bodies, implying different evolution of HML-5 LTRs and genes. Sequence analysis indicated that the proviruses formed approximately 55 million years ago. Accordingly, HML-5 proviral sequences were detected in Old World and New World primates but not in prosimians. No recent activity is associated with this HERV family. We also conclude that the HML-5 consensus sequence primer binding site is identical to methionine tRNA. Therefore, the family should be designated HERV-M. Our study provides important insights into the structure and evolution of the oldest betaretrovirus in the primate genome known to date.

Changes in DNA methylation during mouse embryonic development in relation to X-chromosome activity and imprinting

1990 ◽  
Vol 326 (1235) ◽  
pp. 299-312 ◽  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Embryonic Development ◽  
X Chromosome ◽  
De Novo ◽  
Germ Line ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
Chromatin Configuration ◽  
Methylation Patterns

Changing DNA methylation patterns during embryonic development are discussed in relation to differential gene expression, changes in X-chromosome activity and genomic imprinting. Sperm DNA is more methylated than oocyte DNA, both overall and for specific sequences. The methylation difference between the gametes could be one of the mechanisms (along with chromatin structure) regulating initial differences in expression of parental alleles in early development. There is a loss of methylation during development from the morula to the blastocyst and a marked decrease in methylase activity. De novo methylation becomes apparent around the time of implantation and occurs to a lesser extent in extra-embryonic tissue DNA. In embryonic DNA, de novo methylation begins at the time of random X-chromosome inactivation but it continues to occur after X-chromosome inactivation and may be a mechanism that irreversibly fixes specific patterns of gene expression and X-chromosome inactivity in the female. The germ line is probably delineated before extensive de novo methylation and hence escapes this process. The marked undermethylation of the germ line DNA may be a prerequisite for X-chromosome reactivation. The process underlying reactivation and removal of parent-specific patterns of gene expression may be changes in chromatin configuration associated with meiosis and a general reprogramming of the germ line to developmental totipotency.

scholarly journals Induction of H3K9me3 and DNA methylation by tethered heterochromatin factors in Neurospora crassa

2017 ◽  
Vol 114 (45) ◽  
pp. E9598-E9607 ◽  
Author(s):  
Jordan D. Gessaman ◽  
Eric U. Selker
Keyword(s):  
Dna Methylation ◽  
Gene Silencing ◽  
Neurospora Crassa ◽  
Dna Methyltransferase ◽  
Catalytic Domain ◽  
De Novo ◽  
Histone Deacetylation ◽  
Heterochromatin Formation ◽  
Histone Deacetylase 1

Functionally different chromatin domains display distinct chemical marks. Constitutive heterochromatin is commonly associated with trimethylation of lysine 9 on histone H3 (H3K9me3), hypoacetylated histones, and DNA methylation, but the contributions of and interplay among these features are not fully understood. To dissect the establishment of heterochromatin, we investigated the relationships among these features using an in vivo tethering system in Neurospora crassa. Artificial recruitment of the H3K9 methyltransferase DIM-5 (defective in methylation-5) induced H3K9me3 and DNA methylation at a normally active, euchromatic locus but did not bypass the requirement of DIM-7, previously implicated in the localization of DIM-5, indicating additional DIM-7 functionality. Tethered heterochromatin protein 1 (HP1) induced H3K9me3, DNA methylation, and gene silencing. The induced heterochromatin required histone deacetylase 1 (HDA-1), with an intact catalytic domain, but HDA-1 was not essential for de novo heterochromatin formation at native heterochromatic regions. Silencing did not require H3K9me3 or DNA methylation. However, DNA methylation contributed to establishment of H3K9me3 induced by tethered HP1. Our analyses also revealed evidence of regulatory mechanisms, dependent on HDA-1 and DIM-5, to control the localization and catalytic activity of the DNA methyltransferase DIM-2. Our study clarifies the interrelationships among canonical aspects of heterochromatin and supports a central role of HDA-1–mediated histone deacetylation in heterochromatin spreading and gene silencing.

scholarly journals Dynamic Analysis of Proviral Induction and De Novo Methylation: Implications for a Histone Deacetylase-Independent, Methylation Density-Dependent Mechanism of Transcriptional Repression

2000 ◽  
Vol 20 (3) ◽  
pp. 842-850 ◽  
Author(s):  
Matthew C. Lorincz ◽  
Dirk Schübeler ◽  
Scott C. Goeke ◽  
Mark Walters ◽  
Mark Groudine ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Histone Acetylation ◽  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Mammalian Cells ◽  
Fluorescent Protein ◽  
De Novo ◽  
Trichostatin A ◽  
Histone Deacetylation ◽  
Over Time

ABSTRACT Methylation of cytosines in the CpG dinucleotide is generally associated with transcriptional repression in mammalian cells, and recent findings implicate histone deacetylation in methylation-mediated repression. Analyses of histone acetylation in in vitro-methylated transfected plasmids support this model; however, little is known about the relationships among de novo DNA methylation, transcriptional repression, and histone acetylation state. To examine these relationships in vivo, we have developed a novel approach that permits the isolation and expansion of cells harboring expressing or silent retroviruses. MEL cells were infected with a Moloney murine leukemia virus encoding the green fluorescent protein (GFP), and single-copy, silent proviral clones were treated weekly with the histone deacetylase inhibitor trichostatin A or the DNA methylation inhibitor 5-azacytidine. Expression was monitored concurrently by flow cytometry, allowing for repeated phenotypic analysis over time, and proviral methylation was determined by Southern blotting and bisulfite methylation mapping. Shortly after infection, proviral expression was inducible and the reporter gene and proviral enhancer showed a low density of methylation. Over time, the efficacy of drug induction diminished, coincident with the accumulation of methyl-CpGs across the provirus. Bisulfite analysis of cells in which 5-azacytidine treatment induced GFP expression revealed measurable but incomplete demethylation of the provirus. Repression could be overcome in late-passage clones only by pretreatment with 5-azacytidine followed by trichostatin A, suggesting that partial demethylation reestablishes the trichostatin-inducible state. These experiments reveal the presence of a silencing mechanism which acts on densely methylated DNA and appears to function independently of histone deacetylase activity.

scholarly journals Distribution, Diversity, and Evolution of Endogenous Retroviruses in Perissodactyl Genomes

2018 ◽  
Vol 92 (23) ◽  
Author(s):  
Henan Zhu ◽  
Robert James Gifford ◽  
Pablo Ramiro Murcia
Keyword(s):  
Germ Line ◽  
Mammalian Species ◽  
Endogenous Retroviruses ◽  
Functional Roles ◽  
Physiological Processes ◽  
Great Utility ◽  
White Rhinoceros ◽  
History Of ◽  
Mammalian Genomes

ABSTRACTThe evolution of mammalian genomes has been shaped by interactions with endogenous retroviruses (ERVs). In this study, we investigated the distribution and diversity of ERVs in the mammalian orderPerissodactyla, with a view to understanding their impact on the evolution of modern equids (familyEquidae). We characterize the major ERV lineages in the horse genome in terms of their genomic distribution, ancestral genome organization, and time of activity. Our results show that subsequent to their ancestral divergence from rhinoceroses and tapirs, equids acquired four novel ERV lineages. We show that two of these ERV lineages proliferated extensively in the lineage leading to modern horses, and one contains loci that are actively transcribed in specific tissues. In addition, we show that the white rhinoceros has resisted germ line colonization by retroviruses for more than 54 million years—longer than any other extant mammalian species. The map of equine ERVs that we provide here will be of great utility to future studies aiming to investigate the potential functional roles of equine ERVs and their impact on equine evolution.IMPORTANCEERVs in the host genome are highly informative about the long-term interactions of retroviruses and hosts. They are also interesting because they have influenced the evolution of mammalian genomes in various ways. In this study, we derive a calibrated timeline describing the process through which ERV diversity has been generated in the equine germ line. We determined the distribution and diversity of perissodactyl ERV lineages and inferred their retrotranspositional activity during evolution, thereby gaining insight into the long-term coevolutionary history of retroviruses and mammals. Our study provides a platform for future investigations to identify equine ERV loci involved in physiological processes and/or pathological conditions.

scholarly journals Domestic chickens activate a piRNA defense against avian leukosis virus

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Yu Huining Sun ◽  
Li Huitong Xie ◽  
Xiaoyu Zhuo ◽  
Qiang Chen ◽  
Dalia Ghoneim ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Base Pair ◽  
Domestic Fowl ◽  
De Novo ◽  
Germ Line ◽  
Avian Leukosis Virus ◽  
Endogenous Retroviruses ◽  
Poultry Industry ◽  
Genomic Locus ◽  
Know How

PIWI-interacting RNAs (piRNAs) protect the germ line by targeting transposable elements (TEs) through the base-pair complementarity. We do not know how piRNAs co-evolve with TEs in chickens. Here we reported that all active TEs in the chicken germ line are targeted by piRNAs, and as TEs lose their activity, the corresponding piRNAs erode away. We observed de novo piRNA birth as host responds to a recent retroviral invasion. Avian leukosis virus (ALV) has endogenized prior to chicken domestication, remains infectious, and threatens poultry industry. Domestic fowl produce piRNAs targeting ALV from one ALV provirus that was known to render its host ALV resistant. This proviral locus does not produce piRNAs in undomesticated wild chickens. Our findings uncover rapid piRNA evolution reflecting contemporary TE activity, identify a new piRNA acquisition modality by activating a pre-existing genomic locus, and extend piRNA defense roles to include the period when endogenous retroviruses are still infectious.

scholarly journals Ovarian Stem Cells–-the Pros and Cons

2013 ◽  
Vol 7 ◽  
pp. CMRH.S11086 ◽  
Author(s):  
Ayelet Evron ◽  
Zeev Blumenfeld
Keyword(s):  
Stem Cells ◽  
Cell Biology ◽  
De Novo ◽  
Germ Line ◽  
Mammalian Species ◽  
Primordial Follicle ◽  
Reproductive Age ◽  
Primordial Follicles ◽  
Pros And Cons ◽  
Reproductive Science

The potential for postnatal de novo oogenesis in mammals and in humans has become very controversial in the fields of reproductive science and biology. Historically, it has been thought that females of most mammalian species lose the ability to produce oocytes at birth. A contemporary understanding of stem cell biology together with novel experimental methods has challenged the model of a prenatal fixed ovarian primordial follicle pool that declines with age. Researchers have suggested replenishment of post-natal oocytes by germ-line stem cells (GSCs). According to this theory, GSCs produce oocytes and primordial follicles throughout the lifetime of the adult female. This review describes recent approaches supporting the revolutionary idea of de novo oogenesis in mammals and humans of reproductive-age and provides counter arguments from opponents of this novel and innovative concept.

scholarly journals Dynamic Evolution of De Novo DNA Methyltransferases in Rodent and Primate Genomes

2020 ◽  
Vol 37 (7) ◽  
pp. 1882-1892 ◽  
Author(s):  
Antoine Molaro ◽  
Harmit S Malik ◽  
Deborah Bourc’his
Keyword(s):  
Dna Methylation ◽  
De Novo ◽  
Mammalian Species ◽  
Dna Methyltransferases ◽  
Functional Domain ◽  
Last Common Ancestor ◽  
Diversifying Selection ◽  
Evolutionary Forces ◽  
N Terminus ◽  
Muroid Rodents

Abstract Transcriptional silencing of retrotransposons via DNA methylation is paramount for mammalian fertility and reproductive fitness. During germ cell development, most mammalian species utilize the de novo DNA methyltransferases DNMT3A and DNMT3B to establish DNA methylation patterns. However, many rodent species deploy a third enzyme, DNMT3C, to selectively methylate the promoters of young retrotransposon insertions in their germline. The evolutionary forces that shaped DNMT3C’s unique function are unknown. Using a phylogenomic approach, we confirm here that Dnmt3C arose through a single duplication of Dnmt3B that occurred ∼60 Ma in the last common ancestor of muroid rodents. Importantly, we reveal that DNMT3C is composed of two independently evolving segments: the latter two-thirds have undergone recurrent gene conversion with Dnmt3B, whereas the N-terminus has instead evolved under strong diversifying selection. We hypothesize that positive selection of Dnmt3C is the result of an ongoing evolutionary arms race with young retrotransposon lineages in muroid genomes. Interestingly, although primates lack DNMT3C, we find that the N-terminus of DNMT3A has also evolved under diversifying selection. Thus, the N-termini of two independent de novo methylation enzymes have evolved under diversifying selection in rodents and primates. We hypothesize that repression of young retrotransposons might be driving the recurrent innovation of a functional domain in the N-termini on germline DNMT3s in mammals.

scholarly journals Dynamic evolution of de novo DNA methyltransferases in rodent and primate genomes

2019 ◽  
Author(s):  
Antoine Molaro ◽  
Harmit S. Malik ◽  
Deborah Bourc’his
Keyword(s):  
Dna Methylation ◽  
Gene Conversion ◽  
De Novo ◽  
Mammalian Species ◽  
Dna Methyltransferases ◽  
Functional Domain ◽  
Last Common Ancestor ◽  
Diversifying Selection ◽  
Evolutionary Forces ◽  
N Terminus

AbstractTranscriptional silencing of retrotransposons via DNA methylation is paramount for mammalian fertility and reproductive fitness. During germ cell development, most mammalian species utilize the de novo DNA methyltransferases DNMT3A and DNMT3B to establish DNA methylation patterns. However, many rodent species deploy a third enzyme, DNMT3C, to selectively methylate the promoters of young retrotransposon insertions in their germline. The evolutionary forces that shaped DNMT3C’s unique function are unknown. Using a phylogenomic approach, we confirm here that Dnmt3C arose through a single duplication of Dnmt3B that occurred between 45-71Mya in the last common ancestor of muroid rodents. Most importantly, we reveal that DNMT3C is composed of two independently evolving segments: the latter two-thirds has undergone recurrent gene conversion with Dnmt3B, whereas the N-terminus has not undergone gene conversion and has evolved under strong diversifying selection. We hypothesize that positive selection of Dnmt3C is the result on an ongoing evolutionary arms race with young retrotransposon lineages in muroid genomes. Interestingly, although primates lack DNMT3C, we find that the N-terminus of DNMT3A has also evolved under diversifying selection. Thus, the N-termini of two independent de novo DNMT enzymes have evolved under diversifying selection in rodents and primates. We hypothesize that repression of young retrotransposons might be driving the recurrent innovation of a functional domain in the N-termini on germline DNMTs in mammals.

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