Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transgenerational inheritance of epigenetic signatures at CpG islands in mice

ABSTRACT: Transgenerational epigenetic inheritance in mammals remains a subject of debate. Here we demonstrate that DNA methylation of promoter-associated CpG islands (CGIs) can be transmitted from parents to their offspring in mice. We generated DNA methylation-edited mouse embryonic stem cells (ESCs) in which CGIs of two metabolism related genes, the Ankyrin repeat domain 26 and the low-density lipoprotein receptor, were specifically methylated and silenced. DNA methylation-edited mice generated by microinjection of the methylated ESCs exhibited abnormal metabolic phenotypes. Both the acquired methylation of the targeted CGI and the phenotypic traits were maintained and transmitted across multiple generations. The heritable CGI methylation was subjected to reprograming in parental PGCs and subsequently reestablished in the next generation at post-implantation stages. These observations provide a first concrete step in support of transgenerational epigenetic inheritance in mammals, which may allow for a better understanding of the etiology, diagnosis and prevention of non-genetically inherited human diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE160847 | GEO | 2023/02/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

BANP is an essential transcription factor that opens chromatin and activates CpG island regulated genes

Project description:While the majority of RNA polymerase II initiation events in mammalian genomes take place within CpG island (CGI) promoters, our understanding of their regulation remains limited. Here we combine single-molecule footprinting with interaction proteomics to identify BANP as a critical CGI regulator and the long sought-after TF that binds the orphan CGCG element in mouse and human. We show that BANP drives the activity of essential metabolic genes in the mouse genome in pluripotent and terminally differentiated cells. However, BANP binding is strongly repelled by DNA methylation of its motif in vitro and in vivo, which epigenetically restricts most binding to CGIs and accounts for its absence at aberrantly methylated CGIs in cancer cells. Upon binding to an unmethylated motif, BANP opens chromatin and phases nucleosomes. Our results establish Banp as a critical activator and put forth a model whereby CGI promoter activity relies on methylation-sensitive TFs capable of chromatin opening.

2021-06-16 | PXD024794 | Pride

Genome-wide methylation analysis of AOM/DSS-induced colon tumors

2011-06-30 | GSE21333 | GEO

Genome-wide methylation analysis of AOM/DSS-induced colon tumors

Project description:Genome-wide methylation analysis was performed by methylated DNA immunoprecipitation (MeDIP)-CpG island (CGI) microarray analysis to identify candidate CGIs specifically methylated in mouse colon tumors associated with colitis. We sucessfully identified 23 candidate CGIs methylated in tumors. Two samples were analyzed by MeDIP-CGI microarray. One is a pool of two AOM/DSS-induced colon tumors in BALB/c mice and another is a pool of two normal colonic epithelial cell samples obtained from untreated BALB/c mice by the crypt isolation technique. The pool of normal colonic epithelial cell samples was used as reference. Dye-swaps were not perfromed. The methylation statuses of CGIs identified by microarray were confirmed by another method, methylation-specific PCR.

2011-06-30 | E-GEOD-21333 | biostudies-arrayexpress

Read-through transcription as a general mechanism mediating methylation and silencing of intragenic CGIs [small RNA-seq]

Project description:The human genome contains approximately 27,700 CpG islands (CGIs). Most are associated with promoters and their DNA is nearly always unmethylated. By contrast, CGIs lying within the bodies of genes usually become methylated during differentiation and development. CGIs also normally become methylated at X-inactivated and imprinted genes and abnormally methylated in genome rearrangements and in malignancy. In such circumstances, methylation of CGIs is often associated with RNA transcripts reading through these elements but the relationship of this RNA to methylation of CGIs is not clear. Here we investigated a previously described form of α-thalassemia caused by a genome rearrangement leading to abnormal transcription and DNA methylation of the CGI at the promoter of the α-globin gene. We show that transcription per se is responsible for DNMT3B-mediated methylation of the globin CGI, and that this is a general mechanism responsible for methylation of most intragenic CpG islands.

2017-08-10 | GSE84354 | GEO

Read-through transcription as a general mechanism mediating methylation and silencing of intragenic CGIs [CAP-Seq]

2017-08-10 | GSE84353 | GEO

Read-through transcription as a general mechanism mediating methylation and silencing of intragenic CGIs [H3K36me3_ChIP-seq]

2017-08-10 | GSE84352 | GEO

Cell Type-Specific DNA Methylation at Intragenic CpG Islands in the Immune System (MAP-Seq and ChIP-Seq data)

Project description:Human and mouse genomes contain a similar number of CpG islands (CGIs), which are discrete CpG-rich DNA sequences associated with transcription start sites. In both species, about 50% of all CGIs are remote from annotated promoters, but nevertheless often have promoter-like features. To document the role of CGI methylation in cell differentiation, we analysed DNA methylation at a comprehensive CGI set in cells of the mouse hematopoietic lineage. Using a method that potentially detects ~33% of genomic CpGs in the methylated state (>7 million) we found that large differences in gene expression were accompanied by surprisingly few DNA methylation changes. There were, however, many DNA methylation differences between hematopoietic cells and a distantly related tissue, brain. Altered DNA methylation occurred predominantly at CGIs within gene bodies, which have the properties of cell type-restricted promoters, but infrequently at annotated gene promoters or CGI flanking sequences. Elevated intragenic CGI methylation correlated with silencing of the associated gene. Differentially methylated intragenic CGIs tended to lack H3K4me3 and associate with a transcriptionally repressive environment regardless of methylation state. Our results indicate that DNA methylation changes play a relatively minor role in the late stages of differentiation, but point to a distinct role for intragenic CGIs.

2011-05-23 | GSE25688 | GEO

Cell Type-Specific DNA Methylation at Intragenic CpG Islands in the Immune System (gene expression data)

2011-05-23 | GSE25578 | GEO

Cell Type-Specific DNA Methylation at Intragenic CpG Islands in the Immune System (MAP-Seq and ChIP-Seq data)

2011-05-23 | E-GEOD-25688 | biostudies-arrayexpress

Cell Type-Specific DNA Methylation at Intragenic CpG Islands in the Immune System (gene expression data)

2011-05-23 | E-GEOD-25578 | biostudies-arrayexpress