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

Autor: Deli Liu, Ashley S. Doane, Olivier Elemento, Andrea Sboner, Lesa D. Deonarine, Andries M. Bergman, Elissa W.P. Wong, Noah Dephoure, Mark A. Rubin, Michael A. Augello, Dennis Huang, Mirjam Blattner, Himisha Beltran, Brian D. Robinson, Suzan Stelloo, Christopher E. Barbieri, Wilbert Zwart, Yu Chen
Přispěvatelé: Chemical Biology
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Cancer Research
Transcription
Genetic

Carcinogenesis
interactome
SDG 3 – Goede gezondheid en welzijn
medicine.disease_cause
chromatin remodeling
Tissue Culture Techniques
Prostate cancer
0302 clinical medicine
androgen receptor
610 Medicine & health
Mice
Knockout

prostate cancer
Chromatin
Cell biology
DNA-Binding Proteins
Gene Expression Regulation
Neoplastic

Enhancer Elements
Genetic

Oncology
Cistrome
Receptors
Androgen

030220 oncology & carcinogenesis
Protein Binding
Signal Transduction
Biology
Article
Chromatin remodeling
03 medical and health sciences
SDG 3 - Good Health and Well-being
Cell Line
Tumor

medicine
Animals
Humans
Enhancer
prostate cancer subclass
Homeodomain Proteins
cistrome reprogramming
epigenetics
Tumor Suppressor Proteins
DNA Helicases
PTEN Phosphohydrolase
Prostatic Neoplasms
CHD1
HOXB13
Cell Biology
medicine.disease
Mice
Inbred C57BL

Androgen receptor
030104 developmental biology
Tumor progression
AR
Zdroj: Cancer Cell, 35(4), 603-617.e8. Cell Press
ISSN: 1535-6108
DOI: 10.7892/boris.136289
Popis: 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.
Databáze: OpenAIRE