Supplementary Figure S5 from Transposable Elements Are Co-opted as Oncogenic Regulatory Elements by Lineage-Specific Transcription Factors in Prostate Cancer

Grillo, Giacomo; Keshavarzian, Tina; Linder, Simon; Arlidge, Christopher; Mout, Lisanne; Nand, Ankita; Teng, Mona; Qamra, Aditi; Zhou, Stanley; Kron, Ken J.; Murison, Alex; Hawley, James R.; Fraser, Michael; van der Kwast, Theodorus H.; Raj, Ganesh V.; He, Housheng Hansen; Zwart, Wilbert; Lupien, Mathieu

doi:10.1158/2159-8290.24474050.v1

cd-23-0331_supplementary_figure_s5_suppsf5.pdf (512.02 kB)

Supplementary Figure S5 from Transposable Elements Are Co-opted as Oncogenic Regulatory Elements by Lineage-Specific Transcription Factors in Prostate Cancer

journal contribution

posted on 2023-11-01, 08:01 authored by Giacomo Grillo, Tina Keshavarzian, Simon Linder, Christopher Arlidge, Lisanne Mout, Ankita Nand, Mona Teng, Aditi Qamra, Stanley Zhou, Ken J. Kron, Alex Murison, James R. Hawley, Michael Fraser, Theodorus H. van der Kwast, Ganesh V. Raj, Housheng Hansen He, Wilbert Zwart, Mathieu Lupien

This figure showcases the enrichment of transposable element families in H3K27ac or H3K9kme3 ChIP-seq data generated in benign-like and prostate cancer cell lines. It also includes dCas9-KRAB expression patterns in all CRISPRi clonal cell lines used in this article

Funding

Canadian Institutes of Health Research (IRSC)

History

ARTICLE ABSTRACT

Transposable elements hold regulatory functions that impact cell fate determination by controlling gene expression. However, little is known about the transcriptional machinery engaged at transposable elements in pluripotent and mature versus oncogenic cell states. Through positional analysis over repetitive DNA sequences of H3K27ac chromatin immunoprecipitation sequencing data from 32 normal cell states, we report pluripotent/stem and mature cell state–specific “regulatory transposable elements.” Pluripotent/stem elements are binding sites for pluripotency factors (e.g., NANOG, SOX2, OCT4). Mature cell elements are docking sites for lineage-specific transcription factors, including AR and FOXA1 in prostate epithelium. Expanding the analysis to prostate tumors, we identify a subset of regulatory transposable elements shared with pluripotent/stem cells, including Tigger3a. Using chromatin editing technology, we show how such elements promote prostate cancer growth by regulating AR transcriptional activity. Collectively, our results suggest that oncogenesis arises from lineage-specific transcription factors hijacking pluripotent/stem cell regulatory transposable elements. We show that oncogenesis relies on co-opting transposable elements from pluripotent stem cells as regulatory elements altering the recruitment of lineage-specific transcription factors. We further discover how co-option is dependent on active chromatin states with important implications for developing treatment options against drivers of oncogenesis across the repetitive DNA.This article is featured in Selected Articles from This Issue, p. 2293