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| Status |
Public on Aug 12, 2019 |
| Title |
N6-methyladenosine mRNA marking promotes selective translation of regulons required for human erythropoiesis [crispr] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| 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.
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| Overall design |
Contains 3 Day0 samples representing the initial representation of the ZhangV2 whole genome CRISPR library, 7 Day 12 endpoint samples with all surviving cells, 7 Day 12 endpoint samples enriched for CD235a low or negative cells
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| 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) |
31601799 |
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| Submission date |
Oct 23, 2017 |
| Last update date |
Oct 21, 2019 |
| Contact name |
Sonali Arora |
| E-mail(s) |
sarora@fredhutch.org
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| Organization name |
FHCRC
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| Street address |
1100 Fairview Ave N,
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (17)
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| This SubSeries is part of SuperSeries: |
| GSE106124 |
N6-methyladenosine mRNA marking promotes selective translation of regulons required for human erythropoiesis |
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| Relations |
| BioProject |
PRJNA415385 |
| SRA |
SRP120963 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE105779_RAW.tar |
13.3 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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