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Series GSE147849 Query DataSets for GSE147849
Status Public on Jun 04, 2020
Title Ythdf m6A readers compensate each other in a context dependent manner [RNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary YTH domain family proteins Ythdf1, Ythdf2, Ythdf3 are three readers with highly similar structure, which were shown to have different roles in the cell. However, their similarity and the fact that they tend to bind the same targets suggest that in some cases they may have an overlapping role. In this paper, we systematically knocked-out (KO) each of the three readers and the three together (triple-KO), and estimated the effect in-vitro in mouse embryonic stem cells (mESCs), and in-vivo, in viability and gametogenesis. We show that in mESCs there is a compensation between the three readers, with a dramatic hyper-pluripotent phenotype only in the triple-KO. However, in-vivo, Ythdf2 has a dominant role that cannot be compensated by Ythdf1 or Ythdf3, both in viability of the mouse pups and in gametogenesis. We suggest that compensation is dosage-dependent, and in-vivo we cannot detect it due to difference in the readers’ expression, both in level and in spatial location. In addition, we found that Ythdf1 and Ythdf3 specifically down-regulate 2-cell genes, that Ythdf2-KO in gametogenesis affects microtubuline related genes, and that Mettl3-KO severity is increased as the deletion occurs earlier in gametogenesis.
 
Overall design Four different experiments:
1) Mouse embryonic stem cells were knocked-out to each of the following proteins: Mettl3, Ythdf1, Ythdf2, Ythdf3, and Ythdf1/2/3 triple-KO. RNA-seq was generated in each of these KOs, and in WT.
2) RNA-seq was generated from GV stage oocytes of Mettl3f/f Zp3-Cre+ and Cre- (control) female mice.
3) RNA-seq was generated from post-GV stage oocytes of Ythdf2-/- and Ythdf+/- (control) female mice.
4) RNA-seq was generated from round spermatids of Ythdf2-/- and Ythdf+/+ (control) male mice.
 
Contributor(s) Lasman L, Krupalnik V, Novershtern N, Hanna J
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Submission date Mar 31, 2020
Last update date Jun 04, 2020
Contact name Noa Novershtern
E-mail(s) noa.novershtern@weizmann.ac.il
Organization name Weizmann Institute of Science
Department Molecular Genetics
Street address Weizmann Institute
City Rehovot
ZIP/Postal code 7610001
Country Israel
 
Platforms (1)
GPL21626 NextSeq 550 (Mus musculus)
Samples (27)
GSM4447050 WT mESCs replicate A [mESCs_WT_A_S1]
GSM4447051 WT mESCs replicate B [mESCs_WT_B_S2]
GSM4447052 Ythdf1-/- mESCs replicate A [mESCs_Ythdf1_KO_A_S3]
This SubSeries is part of SuperSeries:
GSE148039 Ythdf m6A readers compensate each other in a context dependent manner
Relations
BioProject PRJNA622277
SRA SRP254797

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE147849_DESeq_Mettl3_oocytes.txt.gz 2.5 Mb (ftp)(http) TXT
GSE147849_DESeq_Ythdf2_oocytes.txt.gz 2.0 Mb (ftp)(http) TXT
GSE147849_DESeq_Ythdf2_sperm.txt.gz 1.5 Mb (ftp)(http) TXT
GSE147849_DESeq_mESCs.txt.gz 4.6 Mb (ftp)(http) TXT
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Processed data are available on Series record
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