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Series GSE95372 Query DataSets for GSE95372
Status Public on Aug 12, 2019
Title N6-methyladenosine mRNA marking promotes selective translation of regulons required for human erythropoiesis [RNA-Seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Many of the regulatory features governing erythrocyte specification, maturation, and associated disorders remain enigmatic. To identify new regulators of erythropoiesis, we performed a functional genomic screen for genes affecting expression of the erythroid marker CD235a/GYPA. Among validating hits were genes coding for the N6-methyladenosine (m6A) mRNA methyltransferase (MTase) complex, including, METTL14, METTL3, and WTAP. We found that m6A MTase activity promotes erythroid gene expression programs through selective translation of ~300 m6A marked mRNAs, including those coding for SETD histone methyltransferases, ribosomal components, and polyA RNA binding proteins, and novel genes. Remarkably, loss of m6A marks resulted in dramatic loss of H3K4me3 marks across key erythroid-specific KLF1 transcriptional targets (e.g., Heme biosynthesis genes). Further, each m6A MTase subunit and a subset of their mRNAs targets are required for human erythroid specification in primary bone-marrow derived progenitors. Thus, m6A mRNA marks promote the translation of a network of genes required for human erythropoiesis.
 
Overall design series of gene KOs
 
Contributor(s) Kuppers DA, Arora S, Lim Y, Lim A, Carter L, Corrin P, Plaisier CL, Basom R, Delrow JJ, Wang S, He HH, Torok-Storb B, Hsieh AC, Paddison PJ
Citation(s)
  • Kuppers DA, Arora S, Lim Y, Lim AR et al. N(6)-methyladenosine mRNA marking promotes selective translation of regulons required for human erythropoiesis. Nat Commun 2019 Oct 10;10(1):4596. PMID: 31601799
Submission date Feb 24, 2017
Last update date Oct 21, 2019
Contact name Sonali Arora
E-mail(s) sarora@fredhutch.org
Organization name FHCRC
Street address 1100 Fairview Ave N,
City Seattle
State/province WA
ZIP/Postal code 98109
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (20)
GSM2508206 Sample GATA1 replicate 1
GSM2508207 Sample GATA1 replicate 2
GSM2508208 Sample GATA1 replicate 3
This SubSeries is part of SuperSeries:
GSE106124 N6-methyladenosine mRNA marking promotes selective translation of regulons required for human erythropoiesis
Relations
BioProject PRJNA376775
SRA SRP100709

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
GSE95372_RAW.tar 3.4 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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