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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

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)

Submission date

Dec 15, 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 (3)

GPL18460	Illumina HiSeq 1500 (Homo sapiens)
GPL18573	Illumina NextSeq 500 (Homo sapiens)
GPL24676	Illumina NovaSeq 6000 (Homo sapiens)

Samples (50)

More...

GSM5737308	MOLM13_WT_SETD1A ChIP-Seq
GSM5737309	SETD1AKO_FKBP-SETD1A_DMSO_HA ChIP-Seq
GSM5737310	SETD1AKO_FKBP-SETD1A_DMSO_ATAC ATAC-Seq

GSM5737311	SETD1AKO_FKBP-SETD1A_dTAG_ATAC ATAC-Seq
GSM5737312	SETD1AKO_FKBP-SETD1A_DMSO_K4me3 ChIP-Seq
GSM5737313	SETD1AKO_FKBP-SETD1A_dTAG_K4me3 ChIP-Seq
GSM5737314	SETD1AKO_FKBP-SETD1A_DMSO_RNAP2 ChIP-Seq
GSM5737315	SETD1AKO_FKBP-SETD1A_dTAG_RNAP2 ChIP-Seq
GSM5737316	SETD1AKO_FKBP-SETD1A_DMSO_K36me3 ChIP-Seq
GSM5737317	SETD1AKO_FKBP-SETD1A_dTAG_K36me3 ChIP-Seq
GSM5737318	SETD1AKO_FKBP-SETD1A_DMSO_K79me2 ChIP-Seq
GSM5737319	SETD1AKO_FKBP-SETD1A_dTAG_K79me2 ChIP-Seq
GSM5737320	SETD1AKO_FKBP-SETD1A_DMSO_K27Ac ChIP-Seq
GSM5737321	SETD1AKO_FKBP-SETD1A_dTAG_K27Ac ChIP-Seq
GSM5737322	SETD1AKO_FKBP-SETD1A_DMSO_K4me1 ChIP-Seq
GSM5737323	SETD1AKO_FKBP-SETD1A_dTAG_K4me1 ChIP-Seq
GSM5737324	SETD1AKO_FKBP-SETD1A_DMSO_CTDpS7 ChIP-Seq
GSM5737325	SETD1AKO_FKBP-SETD1A_dTAG_CTDpS7 ChIP-Seq
GSM5737326	SETD1AKO_FKBP-SETD1A_DMSO_CTDpS5 ChIP-Seq
GSM5737327	SETD1AKO_FKBP-SETD1A_dTAG_CTDpS5 ChIP-Seq
GSM5737328	SETD1AKO_FKBP-SETD1A_DMSO_CTDpS2 ChIP-Seq
GSM5737329	SETD1AKO_FKBP-SETD1A_dTAG_CTDpS2 ChIP-Seq
GSM5737330	MOLM13_WT_HA ChIP-Seq
GSM5737331	SETD1AKO_FKBP-SETD1A_dTAG_HA ChIP-Seq
GSM5737332	SETD1AKO_FKBP-SETD1A_DMSO_PAF1 ChIP-Seq
GSM5737333	SETD1AKO_FKBP-SETD1A_dTAG_PAF1 ChIP-Seq
GSM5737334	SETD1AKO_FKBP-SETD1A_DMSO_SPT5 ChIP-Seq
GSM5737335	SETD1AKO_FKBP-SETD1A_dTAG_SPT5 ChIP-Seq
GSM5737336	SETD1AKO_FKBP-SETD1A_DMSO_NELFe ChIP-Seq
GSM5737337	SETD1AKO_FKBP-SETD1A_dTAG_NELFe ChIP-Seq
GSM5737338	SETD1AKO_FKBP-SETD1A_DMSO_9h_K36me3 ChIP-Seq
GSM5737339	SETD1AKO_FKBP-SETD1A_dTAG_1h_K36me3 ChIP-Seq
GSM5737340	SETD1AKO_FKBP-SETD1A_dTAG_3h_K36me3 ChIP-Seq
GSM5737341	SETD1AKO_FKBP-SETD1A_dTAG_6h_K36me3 ChIP-Seq
GSM5737342	SETD1AKO_FKBP-SETD1A_dTAG_9h_K36me3 ChIP-Seq
GSM5737343	SETD1AKO_FKBP-SETD1A_Empty_DMSO_K36me3 ChIP-Seq
GSM5737344	SETD1AKO_FKBP-SETD1A_Empty_dTAG_K36me3 ChIP-Seq
GSM5737345	SETD1AKO_FKBP-SETD1A_WT_DMSO_K36me3 ChIP-Seq
GSM5737346	SETD1AKO_FKBP-SETD1A_WT_dTAG_K36me3 ChIP-Seq
GSM5737347	SETD1AKO_FKBP-SETD1A_dSET_DMSO_K36me3 ChIP-Seq
GSM5737348	SETD1AKO_FKBP-SETD1A_dSET_dTAG_K36me3 ChIP-Seq
GSM5737349	MOLM13iCas9_sgEmpty_H3K36me3 ChIP-Seq
GSM5737350	MOLM13iCas9_sgCCNK_1_H3K36me3 ChIP-Seq
GSM5737351	MOLM13iCas9_sgCCNK_2_H3K36me3 ChIP-Seq
GSM6131821	SETD1AKO_FKBP-SETD1A_DMSO_CTDpY1
GSM6131822	SETD1AKO_FKBP-SETD1A_dTAG_CTDpY1
GSM6443270	SETD1AKO_FKBP-SETD1A_DMSO_1h_RNAP2
GSM6443271	SETD1AKO_FKBP-SETD1A_dTAG_1h_RNAP2
GSM6443272	SETD1AKO_FKBP-SETD1A_DMSO_1h_CTDpS5
GSM6443273	SETD1AKO_FKBP-SETD1A_dTAG_1h_CTDpS5

This SubSeries is part of SuperSeries:

SETD1A regulates transcriptional pause release of heme biosynthesis genes in leukemia

Relations

BioProject

SRA

Download family	Format
SOFT formatted family file(s)	SOFT
MINiML formatted family file(s)	MINiML
Series Matrix File(s)	TXT

Supplementary file	Size	Download	File type/resource
GSE190994_RAW.tar	9.9 Gb	(http)(custom)	TAR (of BIGWIG)
SRA Run Selector
Raw data are available in SRA
Processed data provided as supplementary file

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