E-MTAB-5568 - Epigenetic regulation and transcriptional repression by Tet1 in the early post-implantation mouse embryo: WG Bisulfite sequencing

Status
Submitted on 20 January 2017, last updated on 3 May 2017, released on 15 May 2017
Organism
Mus musculus
Samples (8)
Protocols (5)
Description
The mammalian TET dioxygenases contribute to global waves of DNA demethylation in the zygote and in primordial germ cells, but their involvement during de novo DNA methylation at peri/post-implantation development is unknown. Here, we show novel physiological functions of Tet1 in the pre-primitive streak stage mouse embryo, where it is expressed not only in the primed-state epiblast, but also in the extra-embryonic ectoderm. In the epiblast, Tet1 contributes to DNA methylation patterning, which indirectly results in dominant transcriptional repression involving a Jumonji-family gene Jmjd8. In the extra-embryonic ectoderm, Tet1 suppresses expression of metabolic genes involved in oxidative phosphorylation. These lineage-specific gene repressive functions, involving distinct modes of regulation by DNA methylation, counteract precocious differentiation of the embryo prior to the onset of gastrulation. Such dysregulation in the absence of Tet1 are surprisingly tolerated in an inbred strain but results in full embryonic lethality in non-inbred mice, thus implicating a complex but essential role of Tet1 in normal gestational development. This dataset includes the WGBS/oxWGBS: Methylation and hydroxymethylation profiling of epiblast-like cells (EpiLCs) in presence or absence of TET1. Whole genome bisulfite sequencing and oxidative whole genome bisulfite sequencing were performed on two wt EpiLCs (male) and two TET1 knock-out EpiLCs (one male and one female).
Experiment types
Bisulfite-seq, genetic modification design
Contact
Citations
Lineage-specific functions of TET1 in the post-implantation mouse embryo. Dr. Rita Khoueiry , Dr. Abhishek Sohni , Dr. Bernard Thienpont , Miss Michela Bartoccetti , Mr. Xinlong Luo , Mr. Joris Vande Velde , Dr. Bram Boeckx , Prof. An Zwijsen , Dr. Anjana Rao , Prof. Diether Lambrechts, Prof Kian Peng Koh.
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
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