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Series GSE59073 Query DataSets for GSE59073
Status Public on Nov 07, 2014
Title Identification of epigenetic barrier that prevents reprogramming in somatic cell nuclear transfer
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Mammalian oocytes can reprogram somatic cells into totipotent state, which allows animal cloning through somatic cell nuclear transfer (SCNT). However, the great majority of SCNT embryos fail to develop to term due to poorly defined reprogramming defects. Here we demonstrate that histone H3 lysine 9 trimethylation (H3K9me3) in donor nuclei is a major epigenetic barrier that prevents efficient nuclear reprogramming in mouse oocytes. Comparative transcriptome analysis of early embryos revealed reprogramming resistant regions (RRRs) where transcriptional activation at 2-cell embryos is inhibited by SCNT compared to in vitro fertilization (IVF). RRRs significantly overlap with H3K9me3 enrichment in donor somatic cells. Importantly, removal of the H3K9me3 by ectopic expression of an H3K9me3 demethylase Kdm4d in recipient oocytes not only reactivates most RRRs, but also greatly improves development of SCNT embryos. Furthermore, the use of Suv39h1/2-depleted somatic nuclei as donors also greatly improves the development of SCNT embryos. Our study thus reveals H3K9me3 as an epigenetic barrier in SCNT-mediated reprogramming and provides a feasible method for improving mammalian cloning efficiency.
Overall design Here we perform RNA-seq based transcriptome profiling in Donor (cumulus cells), in vitro fertilized (IVF) embryos at 1- and 2-cell stages, somatic cell nuclear transfer (SCNT) embryos at 1- and 2-cell stages, Kdm4d over-expressed 2-cell SCNT embryos, and catalytic domain mutated Kdm4d over-expressed 2-cell SCNT embryos with duplicates. 
Contributor(s) Matoba S, Liu Y, Zhang Y
Citation(s) 25417163
Submission date Jul 03, 2014
Last update date May 15, 2019
Contact name Yuting Liu
Organization name Harvard Medical School
Department Department of Genetics
Lab Yi Zhang lab
Street address 82 Walnut St. Unit 3
City Brookline
State/province MA
ZIP/Postal code 02445
Country USA
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (14)
GSM1426195 Donor_1_RNAseq
GSM1426196 Donor_2_RNAseq
GSM1426197 IVF1C_1_RNAseq
BioProject PRJNA254327
SRA SRP044043

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Supplementary file Size Download File type/resource
GSE59073_SupTable_all_genes_fpkm_140630.txt.gz 1.3 Mb (ftp)(http) TXT
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