Need Help?

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.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001003461 Illumina HiSeq 2000 38
Publications Citations
Integrative epigenetic taxonomy of primary prostate cancer.
Nat Commun 9: 2018 4900