Tanget al., Science 376 , eabe1505 (2022) 27 May 2022 9of13
WANG_YAP_TAZ_TARGETSNES = -1.79
FDR = 0.001
Enrichment score (ES)
D
F
FOSL1 KD TAZ KD YAP KD YAP/TAZ KD
CRPC-SCL peaks CRPC-AR peaks
CRPC-AR peaks
CRPC-SCL peaks
A C
B YA P/TAZ KD in MSKPCa3
VINCULIN
YAP
TAZ
FOSL1
NT ctrlYAP
KD
TAZ
KD
YA P
/TAZ
KD
01234
0
2
4
6
MSKPCa3 (CRPC-SCL)
Days
RLU (normalized to day 0)
NT ctrl
YAP KD
TAZ KD
YAP/TAZKD
siDeath
********
**
Chromatin accessibility of MSKPCa3 upon knockdown
GSEA of MSKPCa3 upon knockdown
Coverage on
peaks (bpm)
YA PTAZCTGFCYR6^1
AJUBAANKRD1CCND
1
FOSL1
0.0
0.5
1.0
1.5
2.0
Relative expression
qPCR uponYA P/TAZ KD in MSKPCa3 (48h)
01234
0.0
0.5
1.0
1.5
2.0
2.5
Days
RL
U(
normalized to day 0)
-2.0 Peak center2.0Kb
0.0
0.2
0.4
Coverage on peaks (bpm)
-2.0 Peak center2.0Kb -2.0 Peak center2.0Kb -2.0 Peak center2.0Kb -2.0 Peak center2.0Kb
-2.0 Peak center2.0Kb -2.0 Peak center2.0Kb -2.0 Peak center2.0Kb -2.0 Peak center2.0Kb -2.0 Peak center2.0Kb
0.0
0.1
0.2
0.3
0.4
Control
FOSL
1 KDTAZ KDYAP KD
YAP/
TAZ KD
-30%
-20%
-10%
0%
10%
20%
% of chromatin accessibilitychange compared to contro
l
***
***
***
Chromatin accessibility change
compared to control
CRPC-AR peaks
CRPC-SCL peaks WANG_YAP_TAZ_TARGETSNES = -1.86
FDR = 0.003
Enrichment score (ES)
WANG_YAP_TAZ_TARGETSNES = -1.86
FDR = 0.002
Enrichment score (ES)
WANG_YAP_TAZ_TARGETSNES = -1.67
FDR = 0.04
Enrichment score (ES)
Enrichment score (ES)
FOSL1 KD TAZ KD YAP KD YAP/TAZ KD
E
** **
*
***
**** * **
*
** **** *
*
MSKPCa2 (CRPC-AR)
NT ctrl
YAP KD
TAZ KD
YAP/TAZKD
siDeath
NT ctrl
YAP KD
TAZ KD
YAP /TAZ KD
Fig. 6. Impact ofFOSL1, YAP, TAZ,andYAP/TAZknockdown.(A)qPCR
showing that double knockdown ofYAP/TAZby siRNA in MSKPCa3 leads to
decreased expression of downstream target genes andFOSL1. Mean ± SD,
n = 3. Nontargeting (NT) siRNA serves as the negative control. **P <
0.0001, P <0.01,*P < 0.05 (two-tailed unpairedt test); KD, knockdown.
(B) Western blot (WB) confirming the knockdown efficiency and the decrease
ofFOSL1expression72hoursaftertransfectioninMSKPCa3.(C)Cell
growth curves of MSKPCa3 and MSKPCa2 after siRNA knockdown. Mean ± SD,
n =8forMSKPCa3,n =4forMSKPCa2.****P <0.0001,**P <0.01(two-
tailed unpairedt test). (D) Chromatin accessibility changes uponFOSL1, TAZ,
YAP,andYAP/TAZknockdown at CRPC-ARand CRPC-SCL peaks. (E)Average
percentage of chromatin accessibility changes uponFOSL1, TAZ, YAP,and
YAP/TAZknockdown compared to control at CRPC-AR and CRPC-SCL peaks.
***P < 0.001 (permutation test). (F) GSEA plots showing negative enrichment
of YAP/TAZ target genes in MSKPCa3 upon knockdown ofFOSL1, TAZ,
YAP,andYAP/TAZ.
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