Genome-wide DNA methylation dynamics during epigenetic reprogramming in the porcine germline

Gómez-Redondo, Isabel; Planells, Benjamín; Cánovas, Sebastián; Ivanova, Elena; Kelsey, Gavin

doi:10.1186/s13148-021-01003-x

Cited by 8 publications

(7 citation statements)

References 57 publications

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“…We compared mitotic arrest and the epigenetic reprogramming schedules of chicken germ cells with those well reported for mouse, human, pig, and cattle (Fig. 8 ) [ 17 , 28 , 77 , 78 ]. The mitotic arrest schedule of pigs is as yet unknown, but after sexually dimorphic differentiation, pig germ cell methylation is erased from E28, is minimal at E36, and increases until E42 [ 77 ].…”

Section: Discussionmentioning

confidence: 99%

“…8 ) [ 17 , 28 , 77 , 78 ]. The mitotic arrest schedule of pigs is as yet unknown, but after sexually dimorphic differentiation, pig germ cell methylation is erased from E28, is minimal at E36, and increases until E42 [ 77 ]. Although mouse, human, and cattle methylation schedules differ, in all cases methylation is lowest at the onset of mitotic arrest and increases along the same timeframe.…”

Section: Discussionmentioning

confidence: 99%

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Single-cell RNA sequencing of mitotic-arrested prospermatogonia with DAZL::GFP chickens and revealing unique epigenetic reprogramming of chickens

Choi

Jung

Rengaraj

et al. 2022

J Animal Sci Biotechnol

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Background Germ cell mitotic arrest is conserved in many vertebrates, including birds, although the time of entry or exit into quiescence phase differs. Mitotic arrest is essential for the normal differentiation of male germ cells into spermatogonia and accompanies epigenetic reprogramming and meiosis inhibition from embryonic development to post-hatch. However, mitotic arrest was not well studied in chickens because of the difficulty in obtaining pure germ cells from relevant developmental stage. Results We performed single-cell RNA sequencing to investigate transcriptional dynamics of male germ cells during mitotic arrest in DAZL::GFP chickens. Using differentially expressed gene analysis and K-means clustering to analyze cells at different developmental stages (E12, E16, and hatch), we found that metabolic and signaling pathways were regulated, and that the epigenome was reprogrammed during mitotic arrest. In particular, we found that histone H3K9 and H3K14 acetylation (by HDAC2) and DNA demethylation (by DNMT3B and HELLS) led to a transcriptionally permissive chromatin state. Furthermore, we found that global DNA demethylation occurred gradually after the onset of mitotic arrest, indicating that the epigenetic-reprogramming schedule of the chicken genome differs from that of the mammalian genome. DNA hypomethylation persisted after hatching, and methylation was slowly re-established 3 weeks later. Conclusions We found a unique epigenetic-reprogramming schedule of mitotic-arrested chicken prospermatogonia and prolonged hypomethylation after hatching. This will provide a foundation for understanding the process of germ-cell epigenetic regulation in several species for which this process is not clearly described. Our findings on the biological processes related to sex-specific differentiation of prospermatogonia could help studying germline development in vitro more elaborately.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Single-cell RNA sequencing of mitotic-arrested prospermatogonia with DAZL::GFP chickens and revealing unique epigenetic reprogramming of chickens

Choi

Jung

Rengaraj

et al. 2022

J Animal Sci Biotechnol

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“…The total number of aligned reads and cytosines can be found in Supplementary Table S2 . Methylation levels were quantified using SeqMonk software v1.45.0 by following the pipeline described previously [ 74 ]. GRCm38 Mus musculus genome annotation file was adopted to annotate DMR to genes, and a gene promoter was defined as a region spanning −10 kb and +1kb around the transcription start site (TSS).…”

Section: Methodsmentioning

confidence: 99%

DNA Methylation Analysis Identifies Novel Epigenetic Loci in Dilated Murine Heart upon Exposure to Volume Overload

Elkenani

Tan

et al. 2023

IJMS

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Left ventricular (LV) dilatation, a prominent risk factor for heart failure (HF), precedes functional deterioration and is used to stratify patients at risk for arrhythmias and cardiac mortality. Aberrant DNA methylation contributes to maladaptive cardiac remodeling and HF progression following pressure overload and ischemic cardiac insults. However, no study has examined cardiac DNA methylation upon exposure to volume overload (VO) despite being relatively common among HF patients. We carried out global methylome analysis of LV harvested at a decompensated HF stage following exposure to VO induced by aortocaval shunt. VO resulted in pathological cardiac remodeling, characterized by massive LV dilatation and contractile dysfunction at 16 weeks after shunt. Although methylated DNA was not markedly altered globally, 25 differentially methylated promoter regions (DMRs) were identified in shunt vs. sham hearts (20 hypermethylated and 5 hypomethylated regions). The validated hypermethylated loci in Junctophilin-2 (Jph2), Signal peptidase complex subunit 3 (Spcs3), Vesicle-associated membrane protein-associated protein B (Vapb), and Inositol polyphosphate multikinase (Ipmk) were associated with the respective downregulated expression and were consistently observed in dilated LV early after shunt at 1 week after shunt, before functional deterioration starts to manifest. These hypermethylated loci were also detected peripherally in the blood of the shunt mice. Altogether, we have identified conserved DMRs that could be novel epigenetic biomarkers in dilated LV upon VO exposure.

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“…These erasures allow for totipotency while reestablishment of DNA methylation marks commits cells to a fate. However, DNA methylation of the mouse, pig, and human germlines has been shown to exhibit incomplete erasure, ( Kearns et al, 2000 ; Sutherland et al, 2000 ; Tang et al, 2015 ; Guo et al, 2017 ; Gómez-Redondo et al, 2021 ), with primordial germ cells retaining approximately 10% of their methylation marks ( Seisenberger et al, 2012 ) while the inner cell mass of the blastocyst retains approximately 20% (L. Wang et al, 2014 ). This incomplete erasure indicates that some methylation marks are passed through the germline.…”

Section: Potential Mechanisms For Multigenerational Risk For Asdmentioning

confidence: 99%

The Promise of DNA Methylation in Understanding Multigenerational Factors in Autism Spectrum Disorders

Mouat

LaSalle

2022

Front. Genet.

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Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by impairments in social reciprocity and communication, restrictive interests, and repetitive behaviors. Most cases of ASD arise from a confluence of genetic susceptibility and environmental risk factors, whose interactions can be studied through epigenetic mechanisms such as DNA methylation. While various parental factors are known to increase risk for ASD, several studies have indicated that grandparental and great-grandparental factors may also contribute. In animal studies, gestational exposure to certain environmental factors, such as insecticides, medications, and social stress, increases risk for altered behavioral phenotypes in multiple subsequent generations. Changes in DNA methylation, gene expression, and chromatin accessibility often accompany these altered behavioral phenotypes, with changes often appearing in genes that are important for neurodevelopment or have been previously implicated in ASD. One hypothesized mechanism for these phenotypic and methylation changes includes the transmission of DNA methylation marks at individual chromosomal loci from parent to offspring and beyond, called multigenerational epigenetic inheritance. Alternatively, intermediate metabolic phenotypes in the parental generation may confer risk from the original grandparental exposure to risk for ASD in grandchildren, mediated by DNA methylation. While hypothesized mechanisms require further research, the potential for multigenerational epigenetics assessments of ASD risk has implications for precision medicine as the field attempts to address the variable etiology and clinical signs of ASD by incorporating genetic, environmental, and lifestyle factors. In this review, we discuss the promise of multigenerational DNA methylation investigations in understanding the complex etiology of ASD.

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Genome-wide DNA methylation dynamics during epigenetic reprogramming in the porcine germline

Cited by 8 publications

References 57 publications

Single-cell RNA sequencing of mitotic-arrested prospermatogonia with DAZL::GFP chickens and revealing unique epigenetic reprogramming of chickens

Single-cell RNA sequencing of mitotic-arrested prospermatogonia with DAZL::GFP chickens and revealing unique epigenetic reprogramming of chickens

DNA Methylation Analysis Identifies Novel Epigenetic Loci in Dilated Murine Heart upon Exposure to Volume Overload

The Promise of DNA Methylation in Understanding Multigenerational Factors in Autism Spectrum Disorders

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