scholarly journals Evolution of imprinting via lineage-specific insertion of retroviral promoters

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Aaron B. Bogutz ◽  
Julie Brind’Amour ◽  
Hisato Kobayashi ◽  
Kristoffer N. Jensen ◽  
Kazuhiko Nakabayashi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Endogenous Retroviruses ◽  
The Other ◽  
Imprinted Genes ◽  
Evolutionary Mechanism ◽  
Female Mice ◽  
Parental Allele ◽  
Species Specific ◽  
Human Specific

AbstractImprinted genes are expressed from a single parental allele, with the other allele often silenced by DNA methylation (DNAme) established in the germline. While species-specific imprinted orthologues have been documented, the molecular mechanisms underlying the evolutionary switch from biallelic to imprinted expression are unknown. During mouse oogenesis, gametic differentially methylated regions (gDMRs) acquire DNAme in a transcription-guided manner. Here we show that oocyte transcription initiating in lineage-specific endogenous retroviruses (ERVs) is likely responsible for DNAme establishment at 4/6 mouse-specific and 17/110 human-specific imprinted gDMRs. The latter are divided into Catarrhini- or Hominoidea-specific gDMRs embedded within transcripts initiating in ERVs specific to these primate lineages. Strikingly, imprinting of the maternally methylated genes Impact and Slc38a4 was lost in the offspring of female mice harboring deletions of the relevant murine-specific ERVs upstream of these genes. Our work reveals an evolutionary mechanism whereby maternally silenced genes arise from biallelically expressed progenitors.

scholarly journals Evolution of imprinting via lineage-specific insertion of retroviral promoters

2019 ◽  
Author(s):  
Aaron B. Bogutz ◽  
Julie Brind’Amour ◽  
Hisato Kobayashi ◽  
Kristoffer N. Jensen ◽  
Kazuhiko Nakabayashi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Epigenetic Silencing ◽  
Endogenous Retroviruses ◽  
Imprinted Genes ◽  
Old World Monkeys ◽  
Biallelic Expression ◽  
Evolutionary Mechanism ◽  
Parental Allele ◽  
Species Specific ◽  
Human Specific

SummaryImprinted genes are expressed from a single parental allele. In mammals, this unusual mode of transcription generally depends on the epigenetic silencing of one allele by DNA methylation (DNAme) established in the germline. While many species-specific imprinted orthologues have been documented in eutherians, the molecular mechanisms underlying the evolutionary switch from biallelic to imprinted expression are currently unknown. During mouse oogenesis, gametic differentially methylated regions (gDMRs) acquire DNAme in a process guided by transcription. Here we show that transcription initiating in proximal lineage-specific endogenous retroviruses (ERVs) is likely responsible for DNAme established in oocytes at 4/6 mouse-specific and 17/110 human-specific maternal imprinted gDMRs (igDMRs). The latter can be further divided into Catarrhini (Old World monkeys and apes)- or Hominoidea (ape)-specific igDMRs, which are embedded within transcription units initiating in ERVs specific to these primate lineages. Using CRISPR-Cas9 mutagenesis, we deleted the relevant murine-specific ERVs upstream of the maternally methylated genes Impact and Slc38a4. Strikingly, imprinting at these genes was lost in the offspring of females harboring these deletions and biallelic expression was observed. Our work reveals a novel evolutionary mechanism whereby maternally silenced genes arise from biallelically expressed progenitors.

scholarly journals ZFP57 dictates allelic expression switch of target imprinted genes

2021 ◽  
Vol 118 (5) ◽  
pp. e2005377118
Author(s):  
Weijun Jiang ◽  
Jiajia Shi ◽  
Jingjie Zhao ◽  
Qiu Wang ◽  
Dan Cong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Notch Signaling ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Mouse Embryos ◽  
The Other ◽  
Allelic Expression ◽  
Monoallelic Expression ◽  
Imprinted Genes ◽  
Parent Of Origin

ZFP57 is a master regulator of genomic imprinting. It has both maternal and zygotic functions that are partially redundant in maintaining DNA methylation at some imprinting control regions (ICRs). In this study, we found that DNA methylation was lost at most known ICRs in Zfp57 mutant embryos. Furthermore, loss of ZFP57 caused loss of parent-of-origin–dependent monoallelic expression of the target imprinted genes. The allelic expression switch occurred in the ZFP57 target imprinted genes upon loss of differential DNA methylation at the ICRs in Zfp57 mutant embryos. Specifically, upon loss of ZFP57, the alleles of the imprinted genes located on the same chromosome with the originally methylated ICR switched their expression to mimic their counterparts on the other chromosome with unmethylated ICR. Consistent with our previous study, ZFP57 could regulate the NOTCH signaling pathway in mouse embryos by impacting allelic expression of a few regulators in the NOTCH pathway. In addition, the imprinted Dlk1 gene that has been implicated in the NOTCH pathway was significantly down-regulated in Zfp57 mutant embryos. Our allelic expression switch models apply to the examined target imprinted genes controlled by either maternally or paternally methylated ICRs. Our results support the view that ZFP57 controls imprinted expression of its target imprinted genes primarily through maintaining differential DNA methylation at the ICRs.

Genetic potential for residual feed intake and diet fed during early- to mid-gestation influences post-natal DNA methylation of imprinted genes in muscle and liver tissues in beef cattle

2021 ◽  
Author(s):  
Julia Devos ◽  
Amir Behrouzi ◽  
Francois Paradis ◽  
Christina Straathof ◽  
Changxi Li ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Beef Cattle ◽  
Feed Intake ◽  
Repeated Measures ◽  
Molecular Mechanisms ◽  
Maternal Diet ◽  
Residual Feed Intake ◽  
Imprinted Genes ◽  
Restricted Diet ◽  
Genetic Potential

Abstract Discovery of epigenetic modifications associated with feed efficiency or other economically important traits would increase our understanding of the molecular mechanisms underlying these traits. In combination with known genetic markers, this would provide opportunity to improve genomic selection accuracy in cattle breeding programs. It would also allow cattle to be managed to improve favorable gene expression. The objective of this study was to identify variation in DNA methylation between beef cattle of differential pre-natal nutrition and divergent genetic potential for residual feed intake (RFI). Purebred Angus offspring with the genetic potential for either high (HRFI) or low (LRFI) RFI, were prenatally exposed to either a restricted maternal diet of 0.5 kg/d average daily gain (ADG) or a moderate maternal diet of 0.7 kg/d ADG from 30 to 150 days of gestation. We performed DNA methylation analysis of differentially methylated regions (DMR) of imprinted genes (Insulin-like growth factor 2 (IGF2) DMR2, IGF2/H19 imprinting control region (ICR) and IGF2 receptor (IGF2R) DMR2) using post-natal samples of longissimus dorsi (LD) muscle taken from male and female calves at birth and weaning, and of LD muscle, semimembranosus (SM) muscle and liver samples collected from steers at slaughter (17 months of age). Interestingly, for all three DMR investigated in liver, LRFI steers had higher levels of methylation than HRFI steers. In LD muscle, IGF2/H19 ICR methylation differences for heifers at birth were due to pre-natal diet, while for steers at birth they were mostly the result of genetic potential for RFI with LRFI steers again having higher levels of methylation than HRFI steers. While results from repeated measures analysis of DNA methylation in steers grouped by RFI revealed few differences, in steers grouped by diet, we found higher methylation levels of IGF2 DMR2 and IGF2R DMR2 in LD muscle of restricted diet steers at weaning and slaughter than at birth, as well as increased methylation in LD muscle of restricted diet steers compared to moderate diet steers at weaning and/or slaughter. Our results suggest that differential pre-natal nutrition, and divergent genetic potential for RFI, induces tissue- and sex-specific alterations in post-natal IGF2 and IGF2R methylation patterns and that these patterns can vary with age in Angus beef cattle.

scholarly journals Gene expression and epigenetics reveal species-specific mechanisms acting upon common molecular pathways in the evolution of task division in bees

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Natalia de Souza Araujo ◽  
Maria Cristina Arias
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Bombus Terrestris ◽  
Distinct Species ◽  
Molecular Pathways ◽  
Task Specialization ◽  
Nucleotide Context ◽  
Tetragonisca Angustula ◽  
Species Specific

AbstractA striking feature of advanced insect societies is the existence of workers that forgo reproduction. Two broad types of workers exist in eusocial bees: nurses who care for their young siblings and the queen, and foragers who guard the nest and forage for food. Comparisons between these two worker subcastes have been performed in honeybees, but data from other bees are scarce. To understand whether similar molecular mechanisms are involved in nurse-forager differences across distinct species, we compared gene expression and DNA methylation profiles between nurses and foragers of the buff-tailed bumblebee Bombus terrestris and the stingless bee Tetragonisca angustula. These datasets were then compared to previous findings from honeybees. Our analyses revealed that although the expression pattern of genes is often species-specific, many of the biological processes and molecular pathways involved are common. Moreover, the correlation between gene expression and DNA methylation was dependent on the nucleotide context, and non-CG methylation appeared to be a relevant factor in the behavioral changes of the workers. In summary, task specialization in worker bees is characterized by a plastic and mosaic molecular pattern, with species-specific mechanisms acting upon broad common pathways across species.

scholarly journals Multiple lineages, same molecular basis: task specialization is commonly regulated across all eusocial bee groups

2020 ◽  
Author(s):  
Natalia de Souza Araujo ◽  
Maria Cristina Arias
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Bombus Terrestris ◽  
Distinct Species ◽  
Task Specialization ◽  
Nucleotide Context ◽  
Tetragonisca Angustula ◽  
Gene Expression Correlation ◽  
Species Specific

AbstractA striking feature of advanced insect societies is the existence of workers that forgo reproduction. Two broad types of workers exist in eusocial bees: nurses which care for their young siblings and the queen, and foragers who guard the nest and forage for food. Comparisons between this two worker subcastes have been performed in honeybees, but data from other bees are scarce. To understand whether similar molecular mechanisms are involved in nurse-forager differences across distinct species, we compared gene expression and DNA methylation profiles between nurses and foragers of the buff-tailed bumblebee Bombus terrestris and of the stingless bee Tetragonisca angustula. These datasets were then discussed comparatively to previous findings on honeybees. Our analyses revealed that although the expression pattern of genes is often species-specific, many of the biological processes and molecular pathways involved are common. Moreover, DNA methylation and gene expression correlation were dependent on the nucleotide context.

scholarly journals Genomic imprinting and cancer: Remembering the parental origin

2010 ◽  
Vol 32 (5) ◽  
pp. 26-29
Author(s):  
Adele Murrell ◽  
Santiago Uribe-Lewis
Keyword(s):  
Dna Methylation ◽  
Genomic Imprinting ◽  
Histone Modifications ◽  
Germ Cells ◽  
Parental Origin ◽  
Imprinted Genes ◽  
Parental Allele ◽  
Paternal Line ◽  
Specific Manner ◽  
Parental Copy

Genomic imprinting results in only one copy of a diploid pair of alleles being expressed in a parentof-origin-specific manner. The ‘imprint’ encodes a memory of whether a gene came through the maternal or paternal line and contains the information that decides which parental copy will be active or silent. Imprints are established in the developing gametes, passed on to the next generation after fertilization where they are read and maintained in the somatic cells or erased and reset in the germ cells. The components of the ‘memory’ are a combination of epigenetic features such as DNA methylation, post-translational histone modifications and protein/RNA factors that can bind to DNA and label the genes such that a cell's transcription machinery can distinguish between maternal and paternal alleles. Most imprinted genes are associated with sequences that are methylated on only one parental allele, known as differentially methylated regions (DMRs).

Genomic imprinting and human disease

2010 ◽  
Vol 48 ◽  
pp. 187-200 ◽  
Author(s):  
Ryutaro Hirasawa ◽  
Robert Feil
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Genomic Imprinting ◽  
Developmental Disorders ◽  
Molecular Mechanisms ◽  
Germ Line ◽  
Imprinted Genes ◽  
Foetal Growth ◽  
Sequence Elements ◽  
Covalent Modifications

In many epigenetic phenomena, covalent modifications on DNA and chromatin mediate somatically heritable patterns of gene expression. Genomic imprinting is a classical example of epigenetic regulation in mammals. To date, more than 100 imprinted genes have been identified in humans and mice. Many of these are involved in foetal growth and deve lopment, others control behaviour. Mono-allelic expression of imprinted genes depends on whether the gene is inherited from the mother or the father. This remarkable pattern of expression is controlled by specialized sequence elements called ICRs (imprinting control regions). ICRs are marked by DNA methylation on one of the two parental alleles. These allelic marks originate from either the maternal or the paternal germ line. Perturbation of the allelic DNA methylation at ICRs is causally involved in several human diseases, including the Beckwith–Wiedemann and Silver–Russell syndromes, associated with aberrant foetal growth. Perturbed imprinted gene expression is also implicated in the neuro-developmental disorders Prader–Willi syndrome and Angelman syndrome. Embryo culture and human-assisted reproduction procedures can increase the occurrence of imprinting-related disorders. Recent research shows that, besides DNA methylation, covalent histone modifications and non-histone proteins also contribute to imprinting regulation. The involvement of imprinting in specific human pathologies (and in cancer) emphasizes the need to further explore the underlying molecular mechanisms.

scholarly journals Lifetime Ultraviolet Radiation Exposure and Dna Methylation In Blood Leukocytes: The Norwegian Women And Cancer Study

2019 ◽  
Author(s):  
Christian M Page ◽  
Vera Djordjilović ◽  
Therese H Nøst ◽  
Reza Ghiasvand ◽  
Torkjel M Sandanger ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Ultraviolet Radiation ◽  
Molecular Mechanisms ◽  
Indoor Tanning ◽  
The Other ◽  
Data Set ◽  
Global Methylation ◽  
Cpg Sites ◽  
Genome Wide ◽  
A Genome

Abstract Background Ultraviolet radiation (UVR) exposure is a leading cause of skin cancers and an ubiquitous environmental exposure. However, the molecular mechanisms relating UVR exposure to melanoma is not fully understood. We aimed to investigate if lifetime UVR exposure influences DNA methylation, and if individual CpG sites could be robustly associated with UVR exposures.Methods We assessed DNA methylation in whole blood in three data sets (N = 183, 191, and 125) from the Norwegian Women and Cancer cohort, using Illumina methylation platforms (450k & EPIC). We studied genome-wide DNA methylation, targeted analyses of CpG sites indicated in the literature, global methylation (average over all CpGs and imputation of LINE-1 specific CpGs), and accelerated aging. Lifetime history of UVR exposure (residential ambient UVR, sunburns, sunbathing vacations and indoor tanning) was collected by questionnaires. Cumulative UVR exposure was calculated by adding sunbathing vacations and indoor tanning. We used one data set for discovery and the other two for replication. Results One CpG site showed a genome-wide significant association between cumulative UVR exposure and DNA methylation (cg01884057) (pnominal=3.96e-08), but was not replicated in any of the two replication sets (pnominal≥0.42). Four CpG sites (cg05860019, cg00033666, cg18984282, cg25792367) showed suggestive associations with the other UVR exposures. Conclusion We performed extensive analyses of the association between long-term UVR exposure and DNA methylation in lymphocytes. There was no indication of a robust effect of past UVR exposure on DNA methylation, and our results do not suggest mediation of UVR effects on melanoma risk by DNA methylation.

HUMAN URINARY GONADOTROPHINS ASSAYED BY DIFFERENT RESPONSES IN THE SAME ANIMAL

1960 ◽  
Vol XXXIV (III) ◽  
pp. 375-389 ◽  
Author(s):  
P. S. Brown
Keyword(s):  
Postmenopausal Women ◽  
Ovarian Response ◽  
The Other ◽  
Relative Potency ◽  
Vaginal Opening ◽  
Serial Sections ◽  
Immature Female ◽  
Female Mice ◽  
Marked Disparity ◽  
Relative Potencies

ABSTRACT Selected human urinary gonadotrophins were assayed against one another using various measures of response in the same immature female mice. Intact or hypophysectomized animals were used and in some experiments the results of hypophysectomy were checked in complete serial sections. Extracts from the urine of two subjects with Turner's syndrome were compared. In intact mice, the relative potency judged by the ovarian response differed from that shown by the uterine response and the 95 % fiducial limits of the two estimates did not overlap. When the mice were hypophysectomized, one extract became much less potent while the other did not. Similar differences were shown in the response of intact mice to urinary extracts from two subjects with Klinefelter's syndrome. There was a marked disparity between the relative potencies shown by the uterine response and by the incidence of vaginal opening. Similar differences were not shown between the responses to different extracts from the urine of normal postmenopausal women, but these extracts were known to differ little in quality. The results are interpreted in terms of qualitative differences between human urinary gonadotrophins.

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