KEY RESOURCES TABLE

REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Anti-NCOR2, rabbit polyclonal	Abcam	Cat# ab24551, RRID:AB_2149134
Anti-NCOR2, rabbit monoclonal	Cell Signaling	Cat# 62370, RRID:AB_2799628
Anti-NCOR2, rabbit	Sigma-Aldrich	Cat# HPA001928, RRID:AB_1079454
Normal Rabbit IgG antibody	Cell Signaling	Cat# 2729, RRID:AB_1031062
Normal Rabbit IgG antibody	Santa Cruz	Cat# sc-2027, RRID:AB_737197
Anti-AR, rabbit polyclonal	Millipore	Cat# 06-680
Anti-TBP, rabbit polyclonal	Cell Signaling	Cat# 8515, RRID:AB_10949159
Anti-GAPDH, rabbit monoclonal	Cell Signaling	Cat# 2118, RRID:AB_561053
Anti-beta-actin, rabbit polyclonal	Abcam	Cat# ab8227, RRID:AB_2305186
Rabbit anti-mouse immunoglobulins/HRP antibody	Agilent	Cat# P0161, RRID:AB_2687969
Goat anti-rabbit immunoglobulins/HRP antibody	Agilent	Cat# P0448, RRID:AB_2617138
Ki-67 antibody, rabbit polyclonal	Abcam	Cat# ab15580, RRID:AB_443209
Synaptophysin antibody, rabbit monoclonal	Abcam	Cat# ab52636, RRID:AB_882786
Biological samples
Prostate cancer patient-derived tissue microarrays	Roswell Park	Pathology Resource Network (PRN) and
and de-identified clinical information	Comprehensive Cancer Center	Data Bank Biorepository (DBBR)
Chemicals, peptides, and recombinant proteins
TRIzol RNA Isolation Reagent	Thermo Fisher	Cat# 15596026
AllPrep DNA/RNA/miRNA Universal Kit	QIAGEN	Cat# 80224
iScript cDNA Synthesis Kit	Bio-Rad	Cat# 1708891
5α-Dihydrotestosterone (DHT) solution	Millipore Sigma	Cat# D-073
cOmplete, Mini Protease Inhibitor Cocktail	Millipore Sigma	Cat# 11836153001
Critical commercial assays
TruSeq Stranded Total RNA Library Prep Kit	Illumina	Cat# 20020596
Infinium MethylationEPIC BeadChip Kit	Illumina	Cat# WG-317-1002
ViaLightTM Plus Cell Proliferation and Cytotoxicity BioAssay Kit	Lonza	Cat# LT07-221
TaqMan MicroRNA Reverse Transcription Kit	Applied Biosystems	Cat# 4366596
Turbo DNA-Free kit	Invitrogen	Cat# AM2238
Deposited data
Raw data	This study	GEO: GSE178820 series
Prostate Adenocarcinoma (TCGA, PanCancer Atlas)	TCGA	https://www.cbioportal.org/study/summary?id=prad_tcga_pan_can_atlas_2018
Neuroendocrine Prostate Cancer (Multi-Institute, Nat Med 2016)	Beltran et al., 2016	https://www.cbioportal.org/study/summary?id=nepc_wcm_2016
The Metastatic Prostate Cancer Project	The Metastatic Prostate	https://www.cbioportal.org/study/summary?id=prad_mpcproject_2018
(Provisional, November 2019)	Cancer Project
Metastatic Prostate Cancer (SU2C/PCF Dream Team, Cell 2015)	(Robinson et al., 2015b)	https://www.cbioportal.org/study/summary?id=prad_su2c_2015
Metastatic Prostate Adenocarcinoma (SU2C/PCF Dream Team, PNAS 2019)	Abida et al., 2019	https://www.cbioportal.org/study/summary?id=prad_su2c_2019
Prostate Adenocarcinoma (MSKCC, Cancer Cell 2010)	Tayior et al., 2010	https://www.cbioportai.org/study/ summary?id=prad_mskcc
Prostate Adenocarcinoma (MSKCC/DFCI, Nature Genetics 2018)	Armenia et al., 2018	https://www.cbioportai.org/study/ summary?id=prad_p1000
Experimentai modeis: ceii lines
LNCaP-shControi	This study	N/A
C42-shControi	This study	N/A
LNCaP-shNCOR2-A	This study	N/A
LNCaP-shNCOR2-B	This study	N/A
C42-shNCOR2-A	This study	N/A
C42-shNCOR2-B	This study	N/A
Experimental modeis: organisms/strains
Hsd:Athymic Nude-Foxn1nu, male	Harlan/Envigo	069
CWR22 Prostate Cancer Xenograft Mouse (shControi, shNCOR2; V2LHS-251658)	This study	N/A
Oligonucieotides
NCOR2 (TaqMan Gene Expression Assay)	Thermo Fisher	Assay ID: Hs00196955_m1
AR	Thermo Fisher	Assay ID: Hs00171172_m1
GAPDH (TaqMan Gene Expression Assay)	Thermo Fisher	Assay ID:4326317E
DENND1B (forward: TTACACAATGAAAAGGGAGG)	IDT	N/A
TMPRSS2 (forward: ATGATGCTGCAGCCAGAACAG)	IDT	N/A
HERC3 (forward: AGGTTCTTGTAGGCTGTGGT)	IDT	N/A
CXCR7 (forward: GATGTGGGTTACAAAGCTG)	IDT	N/A
KLK3 (forward: ACTTCAGTGTGTGGACCTTGT)	IDT	N/A
Recombinant DNA
shNCOR2-A (Targeting) pGIPZ Lentiviral Construct	RPCCC Gene Modulation Resource	V2LHS-251658
shNCOR2-B (Targeting) pGIPZ Lentiviral Construct	RPCCC Gene Modulation Resource	V2LHS-196739
GIPZ Lentiviral shRNA Construct	Thermo Fisher	V2LHS
Software and aigorithms
Prism	GraphPad	Version 9.1.0
R V3.6-4.0	https://www.r-project.org/	https://www.r-project.org/
Salmon	Patro et al., 2017	https://combine-lab.github.io/salmon/
Bioconductor 3.2	(Huber et al., 2015)	http://www.bioconductor.org
DESeq2	Love et al., 2014	https://bioconductor.org/packages/release/bioc/html/DESeq2.html
LISA	Qin et al., 2020	http://lisa.cistrome.org/
iRegulon	(Janky et al., 2014)	http://iregulon.aertslab.org/
ChAMP	(Morris et al., 2014)	https://www.bioconductor.org/packages/release/bioc/html/ChAMP.html
DMRcate	Peters et al., 2015	https://www.bioconductor.org/packages/release/bioc/html/DMRcate.html
Rsubread	(Liao et al., 2019)	https://bioconductor.org/packages/release/bioc/html/Rsubread.html
csaw	Lun and Smyth, 2016	https://bioconductor.org/packages/release/bioc/html/csaw.html
MotifDb	Shannon and Richards, 2021	https://bioconductor.org/packages/release/bioc/html/MotifDb.html
HOMER v4.10	Heinz et al., 2010	http://homer.ucsd.edu/homer/
GIGGLE	Layer et al., 2018	https://github.com/ryaniayer/giggie
GSEA v4.1.0	Subramanian et al., 2005	https://www.gsea-msigdb.org/gsea/index.jsp
MSigDB v7.4	Subramanian et al., 2005	https://www.gsea-msigdb.org/gsea/msigdb
ciusterProfiler	Wu et al., 2021	https://bioconductor.org/packages/release/bloc/html/clusterProfiler.html
fgsea	Korotkevich et al., 2019	https://bioconductor.org/packages/release/bioc/html/fgsea.html
Aperio Nuciear Aigorithm	Leica Biosystems	https://www.leicabiosystems.com/digital-pathology/analyze/ihc/aperio-nuclear-algorithm/
ROSE: Rank Ordering of Super Enhancers	Whyte et al., 2013	http://younglab.wi.mit.edu/super_enhancer_code.html
Other
GIBCO, RPMI 1640 Medium	Thermo Fisher	Cat# 11875093
Magna ChIP Protein A+G Magnetic Beads	Sigma-Aidrich	Cat# 16-663