E-GEOD-49763 - Role of Tet1 in genomic imprinting erasure [RRBS-sperm]

Status
Released on 2 December 2013, last updated on 3 June 2014
Organism
Mus musculus
Samples (8)
Protocols (1)
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
Experiment type
methylation profiling by high throughput sequencing 
Contacts
Damian Sendler, Li Shen, Shinpei Yamaguchi, Yi Zhang, Yuting Liu
MINSEQE
Exp. designProtocolsFactorsProcessedSeq. reads
Files
Investigation descriptionE-GEOD-49763.idf.txt
Sample and data relationshipE-GEOD-49763.sdrf.txt
Processed data (1)E-GEOD-49763.processed.1.zip
Links