H3K27ac ChIP-seq in TMPRSS2:ERG positive and negative prostate cancer tissue samples

The TMPRSS2:ERG (T2E) structural rearrangements typifies ~50% of prostate tumors and results in overexpression of the ERG transcription factor. Using chromatin data collected in T2E and non-T2E primary prostate tumors, we show a distinct cis-regulatory landscape between T2E and non-T2E, inclusive of Cluster Of Regulatory Elements (COREs). This is mediated by ERG co-option of HOXB13 and FOXA1 implementing a T2E-specific transcriptional profile. We also report a T2E-specific CORE on the structurally rearranged ERG locus arising from spreading of the TMPRSS2 locus pre-existing CORE, assisting in its overexpression. Finally, we show that the T2E-specific cis-regulatory landscape reveals a vulnerability against the NOTCH pathway. Taken together, our work shows that overexpressed ERG co-opts master transcription factors to deploy a unique cis-regulatory landscape inducing a druggable dependency on NOTCH signaling in T2E prostate tumors.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001003461	H3K27ac ChIP-seq and input genome sequencing was performed in 19 primary prostate tumours classified as intermediate risk. Sequencing of ChIP DNA was performed on an Illumina HiSeq 2000 as either single end 50 bp reads (for 7 samples) or paired end 100 bp reads (for 12 samples). Input DNA from all samples was sequenced using single-end 50 bp reads. The files provided are in fastq format.	Illumina HiSeq 2000	38

Publications	Citations
Integrative epigenetic taxonomy of primary prostate cancer. Stelloo S, Nevedomskaya E, Kim Y, Schuurman K, Valle-Encinas E, Lobo J, Krijgsman O, Peeper DS, Chang SL, Feng FY, Wessels LFA, Henrique R, Jerónimo C, Bergman AM, Zwart W. Nat Commun 9: 2018 4900	79