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Series GSE189893 Query DataSets for GSE189893
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
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 Nov 30, 2021
Last update date Jan 11, 2023
Contact name Masaki Fukuyo
E-mail(s) fukuyo@chiba-u.jp
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 (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (18)
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
This SubSeries is part of SuperSeries:
GSE189894 SETD1A regulates transcriptional pause release of heme biosynthesis genes in leukemia
Relations
BioProject PRJNA784963

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
GSE189893_sample1-12_FPKM.xlsx 57.4 Kb (ftp)(http) XLSX
GSE189893_sample13-18_FPKM.xlsx 1.6 Mb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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