CHD1 Loss Alters AR Binding at Lineage-Specific Enhancers and Modulates Distinct Transcriptional Programs to Drive Prostate Tumorigenesis

Cancer Cell. 2019 Apr 15;35(4):603-617.e8. doi: 10.1016/j.ccell.2019.03.001. Epub 2019 Mar 28.


Deletion of the gene encoding the chromatin remodeler CHD1 is among the most common alterations in prostate cancer (PCa); however, the tumor-suppressive functions of CHD1 and reasons for its tissue-specific loss remain undefined. We demonstrated that CHD1 occupied prostate-specific enhancers enriched for the androgen receptor (AR) and lineage-specific cofactors. Upon CHD1 loss, the AR cistrome was redistributed in patterns consistent with the oncogenic AR cistrome in PCa samples and drove tumor formation in the murine prostate. Notably, this cistrome shift was associated with a unique AR transcriptional signature enriched for pro-oncogenic pathways unique to this tumor subclass. Collectively, these data credential CHD1 as a tumor suppressor in the prostate that constrains AR binding/function to limit tumor progression.

Keywords: AR; CHD1; HOXB13; androgen receptor; chromatin remodeling; cistrome reprogramming; epigenetics; interactome; prostate cancer; prostate cancer subclass.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Carcinogenesis* / genetics
  • Cell Line, Tumor
  • DNA Helicases / deficiency*
  • DNA Helicases / genetics
  • DNA-Binding Proteins / deficiency*
  • DNA-Binding Proteins / genetics
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • PTEN Phosphohydrolase / deficiency
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Protein Binding
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Signal Transduction
  • Tissue Culture Techniques
  • Transcription, Genetic*
  • Tumor Suppressor Proteins / deficiency*
  • Tumor Suppressor Proteins / genetics


  • AR protein, human
  • Chd1 protein, mouse
  • DNA-Binding Proteins
  • HOXB13 protein, human
  • Homeodomain Proteins
  • Receptors, Androgen
  • Tumor Suppressor Proteins
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Pten protein, mouse
  • DNA Helicases
  • CHD1 protein, human