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DNA methylation dynamics of the human pre-implantation embryo

ABSTRACT: We present genome-scale maps of DNA methylation in early human development and perform comparative analysis to mouse that confirm a conserved global erasure of the paternal genome. We find that while many global features of the early embryo are consistent between the two species, the target sequences in which DNA methylation is maintained are distinct. Repetitive elements show a broader range of class specific behaviors in the human embryo and a larger degree of methylation escape in human sperm. We identify thousands of differentially methylated regions (DMRs) that are likely of maternal origin and found that these gamete contributed DMRs are far more species-specific than expected given the conservation of canonical imprint control regions (ICRs). Finally, we extended our studies to the derivation of new human embryonic stem cell (ESC) lines and found notable divergences in DNA methylation signatures from those found in the human embryo and different mouse ESC derivation conditions.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE51239 | GEO | 2014/07/23

SECONDARY ACCESSION(S): PRJNA221793

REPOSITORIES: GEO

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DNA methylation dynamics of the human pre-implantation embryo

Project description:We present genome-scale maps of DNA methylation in early human development and perform comparative analysis to mouse that confirm a conserved global erasure of the paternal genome. We find that while many global features of the early embryo are consistent between the two species, the target sequences in which DNA methylation is maintained are distinct. Repetitive elements show a broader range of class specific behaviors in the human embryo and a larger degree of methylation escape in human sperm. We identify thousands of differentially methylated regions (DMRs) that are likely of maternal origin and found that these gamete contributed DMRs are far more species-specific than expected given the conservation of canonical imprint control regions (ICRs). Finally, we extended our studies to the derivation of new human embryonic stem cell (ESC) lines and found notable divergences in DNA methylation signatures from those found in the human embryo and different mouse ESC derivation conditions. Comparison of DNA methylation patterns in human early development, human ESC derivation and mouse ESC derivation

2014-07-23 | E-GEOD-51239 | biostudies-arrayexpress

Derivation of ground-state female ESCs maintaining gamete-derived DNA methylation

Project description:Inhibitors of MEK1/2 and Gsk3b, known as '2i' culture conditions, enhance the derivation of embryonic stem cells (ESCs) and promote ground-state pluripotency in rodents 1,2. Here we show that the derivation of female mouse ESCs in the presence of 2i (2i-ESCs) results in a widespread loss of DNA methylation including a massive erasure of genomic imprints. Despite this global loss of DNA methylation, the early-passage 2i-ESCs efficiently differentiate into somatic cells and this process requires genome-wide de novo DNA methylation. However, the majority of imprinting control regions (ICRs) remain unmethylated in the 2i-ESC-derived differentiated cells. Consistently, 2i-ESCs exhibit impairment of autonomous embryonic and placental development by tetraploid embryo complementation and nuclear transplantation. We identified the derivation conditions of female ESCs that display 2i-ESC-like transcriptional signatures while preserving gamete-derived DNA methylation and autonomous developmental potential. Upon prolonged culture, however, female ESCs exhibit ICR demethylation, regardless of culture conditions. Our results provide insights into derivation of female ESCs reminiscent of ICM of preimplantation embryos. S-ESCs are ESCs established under serum-containing medium. 2i_S_ESCs are ESCs established in 2i-containing medium, followed by maintenance in serum-containing medium.

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Rhesus macaque cerebral cortex DNA methylation profiling by MeDIP-Chip

Project description:Comparing genetic differences between human and nonhuman primates is a fundamental method to dissect the molecular mechanisms underlying the improved human cognitive ability during evolution. Besides DNA sequence divergences, gene regulation differences between human and nonhuman primates have been shown to be more prominent. DNA methylation is an important type of epigenetic modification that plays critical roles in gene regulations. Trans-generational inheritances of DNA methylation in mammals are widely accepted, suggesting the evolutionary role of DNA methylation. To test if DNA methylation has contributed to the evolution of human brain, with the use of MeDIP-Chip and SEQUENOM MassARRAY, we conducted a systematic analysis to identify the differentially methylated DNA regions (DMRs) between human and rhesus macaque in the cerebral cortex. We first identified a total of 150 candidate DMRs by the MeDIP-Chip method, among which 6 DMRs were confirmed by the SEQUENOM MassARRAY method. And 4 of them were further confirmed using independent samples, while the other 2 were failed to test due to technical difficulties. All the 6 DMRs were in CpG islands or close to CpG islands, and a MIR3 repeat element was located in one DMR, but no repeats was found in the other 5 DMRs. For the 6 DMR genes, most have neural related functions, and their proteins tend to be conserved. Additionally, we found the DNA sequence changes at CpG sites contributed to the species-specific DNA methylation. Our study shed light on the researches of trans-generational epigenetic inheritance and the roles of DNA methylation in evolution, especially human evolution. Compare the DNA methylation levels between human and rhesus macaque

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Human cerebral cortex DNA methylation by MeDIP-Chip

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Identification of maternal imprinting control regions (ICRs) in the post-implantation mouse embryo.

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DNA sequence and chromatin modifiers cooperate to confer epigenetic bistability at imprinting control regions

Project description:DNA methylation is essential for embryonic development and implicated in the regulation of genomic imprinting. Genomic imprinting is established in the germline through parent-specific methylation of distinct cis-regulatory DNA sequences, called imprinting control regions (ICRs). Which factors bind to the opposing chromatin states at ICRs within the same nuclear environment was not systematically addressed. By using a proximity labelling approach with the methylation sensitive transcription factor ZFP57, we identified ATF7IP and other major components of the epigenetic maintenance machinery at ICRs.

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Identification of maternal imprinting control regions (ICRs) in the post-implantation mouse embryo.

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ZFP57 dictates allelic expression switch of target imprinted genes

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