Diagenode

>>>   Click for Diagenode’s approach to COVID-19

Prostate cancer reactivates developmental epigenomic programs during metastatic progression.


Pomerantz MM, Qiu X, Zhu Y, Takeda DY, Pan W, Baca SC, Gusev A, Korthauer KD, Severson TM, Ha G, Viswanathan SR, Seo JH, Nguyen HM, Zhang B, Pasaniuc B, Giambartolomei C, Alaiwi SA, Bell CA, O'Connor EP, Chabot MS, Stillman DR, Lis R, Font-Tello A, Li L,

Epigenetic processes govern prostate cancer (PCa) biology, as evidenced by the dependency of PCa cells on the androgen receptor (AR), a prostate master transcription factor. We generated 268 epigenomic datasets spanning two state transitions-from normal prostate epithelium to localized PCa to metastases-in specimens derived from human tissue. We discovered that reprogrammed AR sites in metastatic PCa are not created de novo; rather, they are prepopulated by the transcription factors FOXA1 and HOXB13 in normal prostate epithelium. Reprogrammed regulatory elements commissioned in metastatic disease hijack latent developmental programs, accessing sites that are implicated in prostate organogenesis. Analysis of reactivated regulatory elements enabled the identification and functional validation of previously unknown metastasis-specific enhancers at HOXB13, FOXA1 and NKX3-1. Finally, we observed that prostate lineage-specific regulatory elements were strongly associated with PCa risk heritability and somatic mutation density. Examining prostate biology through an epigenomic lens is fundamental for understanding the mechanisms underlying tumor progression.

Tags
Antibody

Share this article

Published
July, 2020

Source

Products used in this publication

  • Antibody ChIP-seq grade icon
    C15410196
    H3K27ac Antibody - ChIP-seq Grade
  • Antibody ChIP-seq grade icon
    C15410003-50
    H3K4me3 Antibody - ChIP-seq Grade

       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics