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Status |
Public on Dec 09, 2022 |
Title |
SETD1A regulates transcriptional pause release of heme biosynthesis genes in leukemia [RNA-seq] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Histone methyltransferase SETD1A is critical for acute myeloid leukemia (AML) cell survival, but the molecular mechanism driving SETD1A gene regulation remains elusive. To delineate the role of SETD1A, we utilize a protein degrader technology to induce rapid SETD1A degradation in AML cell lines. SETD1A degradation results in immediate downregulation of transcripts associated with DNA repair and heme biosynthesis pathways. CRISPR-based functional analyses and metabolomics revealed an essential role of SETD1A to maintain mitochondrial respiration in AML cells. These SETD1A targets are enriched in head-to-head (H2H) genes. SETD1A degradation disturbs a non-enzymatic SETD1A domain-dependent cyclin K function, increases the mono-Ser5P RNA polymerase II (RNAP2) at TSS, and induces the promoter-proximal pausing of RNAP2 in a strand-specific manner. This study reveals a non-enzymatic role for SETD1A in transcriptional pause release and provides insight into the mechanism of RNAP2 pausing and its function in cancer.
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Overall design |
1) Examination of SETD1A targets in human MOLM-13 leukemia cell line, 2) Examination of histone modifications and RNAP2 modifications in SETD1A degraded MOLM-13 leukemia cell line. 3) Examination of elongation regulators in SETD1A degraded MOLM-13 leukemia cell line
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Contributor(s) |
Hoshii T, Perlee S, Kikuchi S, Rahmutulla B, Fukuyo M, Masuda T, Ohtsuki S, Soga T, Nabet B, Kaneda A |
Citation(s) |
36450243 |
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Submission date |
Nov 30, 2021 |
Last update date |
Dec 09, 2024 |
Contact name |
Masaki Fukuyo |
E-mail(s) |
fukuyo@chiba-u.jp
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Organization name |
Chiba University
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Department |
Department of Molecular Oncology
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Street address |
1-8-1 Inohana, Chuo-ku
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City |
Chiba |
ZIP/Postal code |
260-8670 |
Country |
Japan |
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Platforms (1) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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Samples (23)
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GSM5709070 |
MOLM-13_SETD1AKO_FKBP-SETD1A_H7_DMSO_d1_exp1 |
GSM5709071 |
MOLM-13_SETD1AKO_FKBP-SETD1A_H7_DMSO_d1_exp2 |
GSM5709072 |
MOLM-13_SETD1AKO_FKBP-SETD1A_F12_DMSO_d1_exp1 |
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This SubSeries is part of SuperSeries: |
GSE189894 |
SETD1A regulates transcriptional pause release of heme biosynthesis genes in leukemia |
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Relations |
BioProject |
PRJNA784963 |