Related Experiment Video

Updated: Jun 21, 2025

An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
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An Atlas of Accessible Chromatin in Advanced Prostate Cancer Reveals the Epigenetic Evolution during Tumor

Raunak Shrestha1,2, Lisa N Chesner1,2, Meng Zhang1,2

  • 1Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.

Cancer Research
|July 11, 2024
PubMed

Insights

Advanced prostate cancer (mCRPC) develops resistance through epigenetic changes. This study maps chromatin accessibility, identifying ZNF263 as a key transcription factor in therapy-resistant subtypes.

Area of Science:

  • Epigenetics and Cancer Biology
  • Genomics and Molecular Oncology

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) is a lethal malignancy driven by androgen signaling.
  • mCRPC develops therapy resistance via androgen receptor (AR) signaling amplification or AR-independent subtypes.
  • Understanding the epigenetic basis of mCRPC subtypes is crucial for identifying resistance mechanisms.

Purpose of the Study:

  • To characterize global chromatin accessibility profiles in mCRPC.
  • To identify lineage-specific transcription factors (TFs) associated with mCRPC subtypes.
  • To elucidate the epigenetic underpinnings of therapy resistance in advanced prostate cancer.

Main Methods:

  • Chromatin accessibility mapping using Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) on 70 mCRPC tissue biopsies.
  • Integration of ATAC-seq data with transcriptome and whole-genome sequencing.
  • Analysis of transcription factor occupancy across accessible chromatin regions.

Main Results:

  • mCRPC exhibits a distinct global chromatin accessibility profile associated with AR function.
  • 203 transcription factors were identified as significantly associated with mCRPC subtypes.
  • ZNF263 was identified as a putative prostate cancer TF, impacting gene activity in the AR-negative, neuroendocrine subtype and potentially activating MYC targets.

Conclusions:

  • The study provides a comprehensive characterization of chromatin accessibility changes in advanced prostate cancer.
  • Identification of subtype-specific TFs offers insights into epigenetic drivers of therapy resistance in mCRPC.
  • ZNF263 emerges as a potential therapeutic target in specific mCRPC subtypes.

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