Genome-wide reprogramming by DNA demethylation during mouse oocyte growth and early development

Key Points Lack of yolk-sac hematopoiesis in the Ldb1−/− mouse results from a decreased number of hemangioblasts and a differentiation block. Identification of genes and pathways regulated by Ldb1 in the hemangioblast reveals potential targets for early developmental manipulation.

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CTCF looping is established during gastrulation in medaka embryos

10.1101/454082 ◽

2018 ◽

Cited By ~ 2

Author(s):

Ryohei Nakamura ◽

Yuichi Motai ◽

Masahiko Kumagai ◽

Haruyo Nishiyama ◽

Neva C. Durand ◽

...

Keyword(s):

Gene Regulation ◽

Embryonic Development ◽

Protein Binding ◽

Early Development ◽

Great Increase ◽

Critical Role ◽

Early Embryogenesis ◽

Genome Architecture ◽

Time Points ◽

Genome Wide

Abstract:Genome architecture plays a critical role in gene regulation, but how the structures seen in mature cells emerge during embryonic development remains poorly understood. Here, we study early development in medaka (the Japanese killifish, Oryzias latipes) at 12 time points before, during, and after gastrulation which is the most dramatic event in early embryogenesis, and characterize transcription, protein binding, and genome architecture. We find that gastrulation is most associated with drastic changes in genome architecture, including the formation of the first loops between sites bound by the insulator protein CTCF and great increase in the size of contact domains. However, the position of CTCF is fixed throughout medaka embryogenesis. Interestingly, genome-wide transcription precedes the emergence of mature domains and CTCF-CTCF loops.

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PHYTOCHROMES B1/B2 ARE KEY REGULATORS OF EPIGENOME REPROGRAMMING DURING TOMATO FRUIT DEVELOPMENT

10.1101/2020.07.30.227447 ◽

2020 ◽

Author(s):

Ricardo Bianchetti ◽

Nicolas Bellora ◽

Luis A de Haro ◽

Rafael Zuccarelli ◽

Daniele Rosado ◽

...

Keyword(s):

Fruit Development ◽

Epigenetic Modification ◽

Tomato Fruit ◽

Dna Demethylation ◽

Temperature Perception ◽

Genome Wide ◽

Fruit Development And Ripening ◽

Histone Modifying Enzymes ◽

Level Of Understanding ◽

Agronomical Traits

AbstractPhytochrome-mediated light and temperature perception has been shown to be a major regulator of fruit development. Furthermore, chromatin remodelling via DNA demethylation has been described as a crucial mechanism behind the fruit ripening process; however, the molecular basis underlying the triggering of this epigenetic modification remains largely unknown. Here, an integrative analyses of the methylome, siRNAome and transcriptome of tomato fruits from phyA and phyB1B2 null mutants was performed, revealing that PHYB1 and PHYB2 influences genome-wide DNA methylation during fruit development and ripening. The experimental evidence indicates that PHYB1B2 signal transduction relies on a gene expression network that includes chromatin organization factors (DNA methylases/demethylases, histone-modifying enzymes and remodelling factors) and transcriptional regulators, ultimately leading to altered mRNA profile of photosynthetic and ripening-associated genes. This new level of understanding provides insights into the orchestration of epigenetic mechanisms in response to environmental cues affecting agronomical traits in fleshy fruits.

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TRIM28 maintains genome imprints and regulates development of porcine SCNT embryos

Reproduction ◽

10.1530/rep-20-0602 ◽

2021 ◽

Vol 161 (4) ◽

pp. 411-424

Author(s):

Yanhui Zhai ◽

Meng Zhang ◽

Xinglan An ◽

Sheng Zhang ◽

Xiangjie Kong ◽

...

Keyword(s):

Somatic Cell Nuclear Transfer ◽

Nuclear Transfer ◽

Transcript Abundance ◽

Dna Demethylation ◽

Epigenetic Variability ◽

Promoter Regions ◽

Cell Stage ◽

Genome Wide ◽

Developmental Progression ◽

Imprinting Gene

Pre-implantation embryos undergo genome-wide DNA demethylation, however certain regions, like imprinted loci remain methylated. Further, the mechanisms ensuring demethylation resistance by TRIM28 in epigenetic reprogramming remain poorly understood. Here, TRIM28 was knocked down in oocytes, and its effects on porcine somatic cell nuclear transfer (SCNT) embryo development was examined. Our results showed that SCNT embryos constructed from TRIM28 knockdown oocytes had significantly lower cleavage (53.9 ± 3.4% vs 64.8 ± 2.7%) and blastocyst rates (12.1 ± 4.3% vs 19.8 ± 1.9%) than control-SCNT embryos. The DNA methylation levels at the promoter regions of the imprinting gene IGF2 and H19 were significantly decreased in the 4-cell stage, and the transcript abundance of other imprinting gene was substantially increased. We also identified an aberrant two-fold decrease in the expression of CXXC1and H3K4me3 methyltransferase (ASH2L and MLL2), and the signal intensity of H3K4me3 had a transient drop in SCNT 2-cell embryos. Our results indicated that maternal TRIM28 knockdown disrupted the genome imprints and caused epigenetic variability in H3K4me3 levels, which blocked the transcription activity of zygote genes and affected the normal developmental progression of porcine SCNT embryos.

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Dnmt1 binds and represses genomic retroelements via DNA methylation in mouse early embryos

Nucleic Acids Research ◽

10.1093/nar/gkaa584 ◽

2020 ◽

Vol 48 (15) ◽

pp. 8431-8444 ◽

Cited By ~ 1

Author(s):

Byungkuk Min ◽

Jung Sun Park ◽

Young Sun Jeong ◽

Kyuheum Jeon ◽

Yong-Kook Kang

Keyword(s):

Dna Methylation ◽

Cpg Islands ◽

Endogenous Retrovirus ◽

Dna Demethylation ◽

Mouse Development ◽

Genome Wide ◽

Early Embryos ◽

Dna Adenine Methylase ◽

Early Mouse ◽

Early Developmental

Abstract Genome-wide passive DNA demethylation in cleavage-stage mouse embryos is related to the cytoplasmic localization of the maintenance methyltransferase DNMT1. However, recent studies provided evidences of the nuclear localization of DNMT1 and its contribution to the maintenance of methylation levels of imprinted regions and other genomic loci in early embryos. Using the DNA adenine methylase identification method, we identified Dnmt1-binding regions in four- and eight-cell embryos. The unbiased distribution of Dnmt1 peaks in the genic regions (promoters and CpG islands) as well as the absence of a correlation between the Dnmt1 peaks and the expression levels of the peak-associated genes refutes the active participation of Dnmt1 in the transcriptional regulation of genes in the early developmental period. Instead, Dnmt1 was found to associate with genomic retroelements in a greatly biased fashion, particularly with the LINE1 (long interspersed nuclear elements) and ERVK (endogenous retrovirus type K) sequences. Transcriptomic analysis revealed that the transcripts of the Dnmt1-enriched retroelements were overrepresented in Dnmt1 knockdown embryos. Finally, methyl-CpG-binding domain sequencing proved that the Dnmt1-enriched retroelements, which were densely methylated in wild-type embryos, became demethylated in the Dnmt1-depleted embryos. Our results indicate that Dnmt1 is involved in the repression of retroelements through DNA methylation in early mouse development.

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FACT complex is required for DNA demethylation at heterochromatin during reproduction in Arabidopsis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1713333115 ◽

2018 ◽

Vol 115 (20) ◽

pp. E4720-E4729 ◽

Cited By ~ 22

Author(s):

Jennifer M. Frost ◽

M. Yvonne Kim ◽

Guen Tae Park ◽

Ping-Hung Hsieh ◽

Miyuki Nakamura ◽

...

Keyword(s):

Genomic Imprinting ◽

Nucleosome Occupancy ◽

Dna Demethylation ◽

Embryo Viability ◽

Chromatin States ◽

Specific Recognition ◽

Genome Wide ◽

Target Sites ◽

Recognition Protein

The DEMETER (DME) DNA glycosylase catalyzes genome-wide DNA demethylation and is required for endosperm genomic imprinting and embryo viability. Targets of DME-mediated DNA demethylation reside in small, euchromatic, AT-rich transposons and at the boundaries of large transposons, but how DME interacts with these diverse chromatin states is unknown. The STRUCTURE SPECIFIC RECOGNITION PROTEIN 1 (SSRP1) subunit of the chromatin remodeler FACT (facilitates chromatin transactions), was previously shown to be involved in the DME-dependent regulation of genomic imprinting in Arabidopsis endosperm. Therefore, to investigate the interaction between DME and chromatin, we focused on the activity of the two FACT subunits, SSRP1 and SUPPRESSOR of TY16 (SPT16), during reproduction in Arabidopsis. We found that FACT colocalizes with nuclear DME in vivo, and that DME has two classes of target sites, the first being euchromatic and accessible to DME, but the second, representing over half of DME targets, requiring the action of FACT for DME-mediated DNA demethylation genome-wide. Our results show that the FACT-dependent DME targets are GC-rich heterochromatin domains with high nucleosome occupancy enriched with H3K9me2 and H3K27me1. Further, we demonstrate that heterochromatin-associated linker histone H1 specifically mediates the requirement for FACT at a subset of DME-target loci. Overall, our results demonstrate that FACT is required for DME targeting by facilitating its access to heterochromatin.

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