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Role of Tet1 in genomic imprinting erasure [RRBS-PGC]

ABSTRACT: Genomic imprinting is an allele-specific gene expression system important for mammalian development and function. The molecular basis of genomic imprinting is allele-specific DNA methylation 2. While it is well known that the de novo DNA methyltransferases Dnmt3a/b are responsible for the establishment of genomic imprinting, how the methylation mark is erased during primordial germ cell (PGC) reprogramming remains a mystery. Here we report that Tet1 plays a critical role in the erasure of genomic imprinting. We show that despite their identical genotype, progenies derived from mating between Tet1-KO males and wild-type females exhibit a number of variable phenotypes including placental, fetal and postnatal growth defects, and early embryonic lethality. These defects are, at least in part, caused by the dysregulation of imprinted genes, such as Peg10 and Peg3, which exhibit aberrant hypermethylation in the paternal allele of differential methylated regions (DMRs). RNA-seq reveals extensive dysregulation of imprinted genes in the next generation due to paternal functional loss of Tet1. Genome-wide DNA methylation analysis of E13.5 PGCs and sperm derived from Tet1-KO mice reveals hypermethylation of DMRs of imprinted genes in sperm, which can be traced back to PGCs. Dynamics of methylation change in Tet1-affected sites suggested that Tet1 swipes remaining methylation including imprinted genes at late reprogramming stage. We also revealed that Tet1play a role in paternal imprinting erasure in females germline. Thus, our study establishes a critical function for Tet1 in the erasure of genomic imprinting. Genome-wide DNA methylation analysis of E13.5 PGCs from control and Tet1-KO mice

ORGANISM(S): Mus musculus

SUBMITTER: Yi Zhang

PROVIDER: E-GEOD-49762 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Role of Tet1 in genomic imprinting erasure [RRBS-sperm]

Project description:Genomic imprinting is an allele-specific gene expression system important for mammalian development and function. The molecular basis of genomic imprinting is allele-specific DNA methylation 2. While it is well known that the de novo DNA methyltransferases Dnmt3a/b are responsible for the establishment of genomic imprinting, how the methylation mark is erased during primordial germ cell (PGC) reprogramming remains a mystery. Here we report that Tet1 plays a critical role in the erasure of genomic imprinting. We show that despite their identical genotype, progenies derived from mating between Tet1-KO males and wild-type females exhibit a number of variable phenotypes including placental, fetal and postnatal growth defects, and early embryonic lethality. These defects are, at least in part, caused by the dysregulation of imprinted genes, such as Peg10 and Peg3, which exhibit aberrant hypermethylation in the paternal allele of differential methylated regions (DMRs). RNA-seq reveals extensive dysregulation of imprinted genes in the next generation due to paternal functional loss of Tet1. Genome-wide DNA methylation analysis of E13.5 PGCs and sperm derived from Tet1-KO mice reveals hypermethylation of DMRs of imprinted genes in sperm, which can be traced back to PGCs. Dynamics of methylation change in Tet1-affected sites suggested that Tet1 swipes remaining methylation including imprinted genes at late reprogramming stage. We also revealed that Tet1play a role in paternal imprinting erasure in females germline. Thus, our study establishes a critical function for Tet1 in the erasure of genomic imprinting. Genome-wide DNA methylation analysis of sperm derived from control and Tet1-KO mice

2013-12-02 | E-GEOD-49763 | biostudies-arrayexpress

Role of Tet1 in genomic imprinting erasure [RNA-seq]

2013-12-02 | E-GEOD-49761 | biostudies-arrayexpress

Role of Tet1 in genomic imprinting erasure [RRBS-sperm]

2013-12-02 | GSE49763 | GEO

Role of Tet1 in genomic imprinting erasure [RRBS-PGC]

2013-12-02 | GSE49762 | GEO

Role of Tet1 in genomic imprinting erasure [RNA-seq]

2013-12-02 | GSE49761 | GEO

Characterization of the Imprinting Signature of Mouse Embryo Fibroblasts by RNA Deep Sequencing

Project description:Mouse embryo fibroblasts (MEFs) closely resemble mouse embryos and are convenient sources for biochemical studies when cell number may be limiting from mouse embryos. To derive the imprinting signature of MEFs and potentially detect novel imprinted genes we characterized them using strand- and allele-specific RNA deep sequencing. We used Sequenom allelotyping in embryo and adult organs to verify parental allele-specific expression patterns. We found correct parental allele-specific transcription of 32 known ubiquitously imprinted genes in MEFs. Our analysis did not reveal any novel imprinted genes in MEFs, but detected extended parental allele-specific transcription in several known imprinted domains: maternal allele-specific transcription downstream of Grb10 and downstream of Meg3, Rtl1as and Rian in the Dlk1-Dio3 cluster, an imprinted domain implicated in development. We detected paternal allele-specific transcription downstream of Nespas, Peg3, Peg12 and Snurf/Snrpn. These imprinted transcript extensions were not unique to MEFs, but were also present in other somatic cells. Their 5’ end points did not carry opposing chromatin marks or parental allele-specific DNA methylation, suggesting that their parental allele-specific transcription is under the control of the extended genes. Based on the imprinting signature of MEFs, they provide valid models for understanding the biochemical aspects of genomic imprinting. Strand-specific and parental allele-specific RNA-seq was done in female mouse embryo fibroblasts.

2013-11-18 | E-GEOD-49538 | biostudies-arrayexpress

Extensive imprinted gene expression in Arabidopsis endosperm

Project description:Some flowering plant and vertebrate genes are expressed primarily or exclusively from either the maternal or paternal allele, a phenomenon called genomic imprinting. Flowering plant imprinted gene expression has been described primarily in endosperm, a terminal nutritive tissue consumed by the embryo during seed development or after germination. Imprinted expression in Arabidopsis thaliana endosperm is orchestrated by differences in cytosine DNA methylation between the paternal and maternal genomes, as well as by Polycomb group (PcG) proteins. Currently only eleven imprinted Arabidopsis genes are known. Here we use extensive sequencing of cDNA libraries to identify many new paternally and maternally imprinted genes in A. thaliana endosperm, including transcription factors, proteins involved in hormone signaling, and epigenetic regulators. The imprinted status of many maternally-expressed genes is not altered by mutations in the DNA-demethylating glycosylase DEMETER, the DNA methyltransferase MET1 or the core PcG protein FIE, indicating that these genes are regulated by novel mechanisms or deposited from maternal tissues. We did not find any imprinted genes in the embryo. Our results demonstrate that imprinted gene expression, particularly from the maternal genome, is an extensive, mechanistically complex phenomenon that likely affects multiple aspects of seed development. Epigenetics Examination of genomic imprinting in Arabidopsis endosperm

2011-03-10 | E-GEOD-24644 | biostudies-arrayexpress

Characterization of the Imprinting Signature of Mouse Embryo Fibroblasts by RNA Deep Sequencing

2013-11-18 | GSE49538 | GEO

Role of Tet1 in genomic imprinting erasure

Project description:Role of Tet1 in genomic imprinting erasure

| PRJNA214850 | ENA

Conserved imprinting associated with unique epigenetic signatures in the Arabidopsis genus

Project description:In plants, imprinted gene expression occurs in endosperm seed tissue and can be associated with differential DNA methylation between maternal and paternal alleles. Imprinting is theorized to have been selected for because of conflict between parental genomes in offspring, but most studies of imprinting have been conducted in Arabidopsis thaliana, an inbred primarily self-fertilizing species that should have limited parental conflict. We examined embryo and endosperm allele-specific expression and DNA methylation genome-wide in the wild outcrossing species Arabidopsis lyrata. Here we show that the majority of A. lyrata imprinted genes exhibit parentally-biased expression in A. thaliana, suggesting that there is evolutionary conservation in gene imprinting. Surprisingly, we discovered substantial interspecies differences in methylation features associated with paternally expressed imprinted genes (PEGs). Unlike A. thaliana, the maternal allele of many A. lyrata PEGs was hypermethylated in the CHG context. Increased maternal allele CHG methylation was associated with increased expression bias in favor of the paternal allele. We propose that CHG methylation maintains or reinforces repression of maternal alleles of PEGs. These data suggest that while the genes subject to imprinting are largely conserved, there is flexibility in the epigenetic mechanisms employed between closely related species to maintain monoallelic expression. This supports the idea that imprinting of specific genes is a functional phenomenon, and not simply a byproduct of seed epigenomic reprogramming.

2016-09-01 | GSE76076 | GEO

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