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Series GSE49762 Query DataSets for GSE49762
Status Public on Dec 02, 2013
Title Role of Tet1 in genomic imprinting erasure [RRBS-PGC]
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary 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.
 
Overall design Genome-wide DNA methylation analysis of E13.5 PGCs from control and Tet1-KO mice
 
Contributor(s) Yamaguchi S, Shen L, Liu Y, Sendler D, Zhang Y
Citation(s) 24291790
Submission date Aug 11, 2013
Last update date May 15, 2019
Contact name Li Shen
Organization name HHMI/Boston Children's Hospital/Harvard Medical School
Street address 200 Longwood Ave
City Boston
ZIP/Postal code 02115
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (4)
GSM1206692 WT-1 PGC
GSM1206693 WT-2 PGC
GSM1206694 Homo-1 PGC
This SubSeries is part of SuperSeries:
GSE49764 Role of Tet1 in genomic imprinting erasure
Relations
BioProject PRJNA214851
SRA SRP028714

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE49762_RAW.tar 12.2 Mb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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