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Series GSE78829

Query DataSets for GSE78829

Status

Public on Oct 25, 2016

Title

Promiscuous targeting of bromodomains by Bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia [set2]

Organism

Experiment type

Expression profiling by array

Summary

Bromodomains (BRDs) have emerged as compelling targets for cancer therapy. The development of selective and potent BET inhibitors and their significant activity in diverse tumor models has rapidly translated into clinical studies and has motivated drug development efforts targeting non-BET BRDs. However, the complex multidomain/subunit architecture of bromodomain protein complexes complicates predictions of consequences of their pharmacological targeting. To address this issue we developed a promiscuous bromodomain inhibitor (bromosporine, BSP) that broadly targets BRDs (including BETs) with nanomolar affinity, creating a tool for the identification of cellular processes and diseases where BRDs have a regulatory function. As a proof of principle we studied the effect of BSP in leukemic cell-lines known to be sensitive to BET inhibition and found as expected strong anti-proliferative activity. Comparison of the modulation of transcriptional profiles by BSP at short inhibitor exposure resulted in a BET inhibitor signature but no significant additional changes in transcription that could account for inhibition of other BRDs. Thus, non-selective targeting of BRDs identified BETs, but not other BRDs, as master regulators of a context dependent primary transcription response.

Overall design

Cells were seeded the day prior to treatment at 2x10^5 per ml. Treatments were performed so that a final concentration of 0.1 % DMSO (Cat.#D1435; Sigma) was achieved and cells were incubated with DMSO or 500 nM test compound (BSP, JQ1, LP99, GSK2801, iCBP112 or OF1) for 6 h prior to isolation of RNA. Total RNA was isolated using a standard TRIzol (Invitrogen) protocol and prepared using RNeasy columns (Cat.#74106 plus; Qiagen). RNA was quantified using a Nanodrop spectrophotometer (model ND1000; Thermo Fisher) and integrity assessed on a BioAnalyzer (2100; Agilent Laboratories, USA). All samples had a RNA Integrity Number (RIN) ≥ 9. Biological triplicates were performed for each condition tested.

Contributor(s)

Filippakopoulos P, Blancher C

Citation(s)

Submission date

Mar 02, 2016

Last update date

Aug 13, 2018

Contact name

Panagis Filippakopoulos

E-mail(s)

panagis.filippakopoulos@gmail.com

Organization name

Oxford University

Department

Nuffield Department of Medicine

Lab

Structural Genomics Consortium

Street address

ORCRB - Roosevelt Drive

City

Oxford

State/province

Oxfordshire

ZIP/Postal code

OX3 7DQ

Country

United Kingdom

Platforms (1)

Illumina HumanHT-12 V4.0 expression beadchip

Samples (42)

More...

GSM2078325	set_2 K562 DMSO Replicate 1
GSM2078326	set_2 K562 DMSO Replicate 2
GSM2078327	set_2 K562 DMSO Replicate 3

GSM2078328	set_2 K562 500 nM BSP Treatment Replicate 1
GSM2078329	set_2 K562 500 nM BSP Treatment Replicate 2
GSM2078330	set_2 K562 500 nM BSP Treatment Replicate 3
GSM2078331	set_2 K562 500 nM JQ1 Treatment Replicate 1
GSM2078332	set_2 K562 500 nM JQ1 Treatment Replicate 2
GSM2078333	set_2 K562 500 nM JQ1 Treatment Replicate 3
GSM2078334	set_2 K562 500 nM LP99 Treatment Replicate 1
GSM2078335	set_2 K562 500 nM LP99 Treatment Replicate 2
GSM2078336	set_2 K562 500 nM LP99 Treatment Replicate 3
GSM2078337	set_2 K562 500 nM GSK2801 Treatment Replicate 1
GSM2078338	set_2 K562 500 nM GSK2801 Treatment Replicate 2
GSM2078339	set_2 K562 500 nM GSK2801 Treatment Replicate 3
GSM2078340	set_2 K562 500 nM iCBP112 Treatment Replicate 1
GSM2078341	set_2 K562 500 nM iCBP112 Treatment Replicate 2
GSM2078342	set_2 K562 500 nM iCBP112 Treatment Replicate 3
GSM2078343	set_2 K562 500 nM OF1 Treatment Replicate 1
GSM2078344	set_2 K562 500 nM OF1 Treatment Replicate 2
GSM2078345	set_2 K562 500 nM OF1 Treatment Replicate 3
GSM2078346	set_2 MV-4-11 DMSO Replicate 1
GSM2078347	set_2 MV-4-11 DMSO Replicate 2
GSM2078348	set_2 MV-4-11 DMSO Replicate 3
GSM2078349	set_2 MV-4-11 500 nM BSP Treatment Replicate 1
GSM2078350	set_2 MV-4-11 500 nM BSP Treatment Replicate 2
GSM2078351	set_2 MV-4-11 500 nM BSP Treatment Replicate 3
GSM2078352	set_2 MV-4-11 500 nM JQ1 Treatment Replicate 1
GSM2078353	set_2 MV-4-11 500 nM JQ1 Treatment Replicate 2
GSM2078354	set_2 MV-4-11 500 nM JQ1 Treatment Replicate 3
GSM2078355	set_2 MV-4-11 500 nM LP99 Treatment Replicate 1
GSM2078356	set_2 MV-4-11 500 nM LP99 Treatment Replicate 2
GSM2078357	set_2 MV-4-11 500 nM LP99 Treatment Replicate 3
GSM2078358	set_2 MV-4-11 500 nM GSK2801 Treatment Replicate 1
GSM2078359	set_2 MV-4-11 500 nM GSK2801 Treatment Replicate 2
GSM2078360	set_2 MV-4-11 500 nM GSK2801 Treatment Replicate 3
GSM2078361	set_2 MV-4-11 500 nM iCBP112 Treatment Replicate 1
GSM2078362	set_2 MV-4-11 500 nM iCBP112 Treatment Replicate 2
GSM2078363	set_2 MV-4-11 500 nM iCBP112 Treatment Replicate 3
GSM2078364	set_2 MV-4-11 500 nM OF1 Treatment Replicate 1
GSM2078365	set_2 MV-4-11 500 nM OF1 Treatment Replicate 2
GSM2078366	set_2 MV-4-11 500 nM OF1 Treatment Replicate 3

This SubSeries is part of SuperSeries:

Promiscuous targeting of bromodomains by Bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia

Relations

BioProject

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
GSE78829_Non-normalized_data.txt.gz	11.1 Mb	(ftp)(http)	TXT
GSE78829_Normalized_data_with_statistics.xlsx	19.9 Mb	(ftp)(http)	XLSX
GSE78829_RAW.tar	26.2 Mb	(http)(custom)	TAR
Processed data included within Sample table
Processed data are available on Series record

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