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Series GSE190994 Query DataSets for GSE190994
Status Public on Dec 09, 2022
Title SETD1A regulates transcriptional pause release of heme biosynthesis genes in leukemia [ChIP-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
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.
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
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
Submission date Dec 15, 2021
Last update date Jan 11, 2023
Contact name Masaki Fukuyo
Organization name Chiba University
Department Department of Molecular Oncology
Street address 1-8-1 Inohana, Chuo-ku
City Chiba
ZIP/Postal code 260-8670
Country Japan
Platforms (3)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (50)
GSM5737308 MOLM13_WT_SETD1A ChIP-Seq
This SubSeries is part of SuperSeries:
GSE189894 SETD1A regulates transcriptional pause release of heme biosynthesis genes in leukemia
BioProject PRJNA789267
SRA SRP351345

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
GSE190994_RAW.tar 9.9 Gb (http)(custom) TAR (of BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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