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Series GSE78138 Query DataSets for GSE78138
Status Public on Feb 23, 2016
Title MLL1 is essential for the senescence-associated secretory phenotype [RNA-Seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Oncogene-induced senescence (OIS) and therapy-induced senescence (TIS), while tumor-suppressive, also promote procarcinogenic effects by activating the DNA damage response (DDR), which in turn induces inflammation. This inflammatory response prominently includes an array of cytokines known as the senescence-associated secretory phenotype (SASP). Previous observations link the transcription-associated methyltransferase and oncoprotein MLL1 to the DDR, leading us to investigate the role of MLL1 in SASP expression. Our findings reveal direct MLL1 epigenetic control over proproliferative cell cycle genes: MLL1 inhibition represses expression of proproliferative cell cycle regulators required for DNA replication and DDR activation, thus disabling SASP expression. Strikingly, however, these effects of MLL1 inhibition on SASP gene expression do not impair OIS and, furthermore, abolish the ability of the SASP to enhance cancer cell proliferation. More broadly, MLL1 inhibition also reduces “SASP-like” inflammatory gene expression from cancer cells in vitro and in vivo independently of senescence. Taken together, these data demonstrate that MLL1 inhibition may be a powerful and effective strategy for inducing cancerous growth arrest through the direct epigenetic regulation of proliferation-promoting genes and the avoidance of deleterious OIS- or TIS-related tumor secretomes, which can promote both drug resistance and tumor progression.
 
Overall design This study consists of a single replicate of RNA-seq from oncogene-induced senescent (or control) IMR90 cells in a MLL1 knockdown (or WT) background, for a total of four samples
 
Contributor(s) Capell BC, Drake AM, Zhu J, Shah PP, Dou Z, Dorsey J, Simola DF, Donahue G, Sammons M, Rai TS, Natale C, Ridky TW, Adams PD, Berger SL
Citation(s) 26833731
Submission date Feb 22, 2016
Last update date May 15, 2019
Contact name Gregory Donahue
Organization name The University of Pennsylvania
Department Cell & Developmental Biology
Lab Zaret Lab
Street address 3400 Civic Center Blvd, Bldg 421
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (4)
GSM2067916 RNA WT Control
GSM2067917 RNA WT OIS
GSM2067918 RNA MLL1 KD Control
This SubSeries is part of SuperSeries:
GSE78142 MLL1 is essential for the senescence-associated secretory phenotype
Relations
BioProject PRJNA312767
SRA SRP070636

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
GSE78138_RAW.tar 61.5 Mb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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