Science - USA (2021-07-16)

310 16 JULY 2021•VOL 373 ISSUE 6552 sciencemag.org SCIENCE

AB

D

E

C

F

−7.5 −5.0 −2.5 0.0 2.5 5.0 7.5 10.0

PC1: 70.79%

−4

−2

0

2

4

6

PC2: 29.21%

cBAF

PBAF

ncBAF

Complex Activity: PC1 vs PC2

Top PC1 loadings:

H4Kpolyac

H4Kpolyac-H3K4me3

H4K20ac-H3K4me3

H4K5ac

H4K16ac-H3K4me3

H3K4me3

H4K16ac

cBAF

PBAF

ncBAF

H4K5ac-H3K4me3H4K5ac-H3K4me3H4K5ac-H3K4me3

H4K5aH4K5aH4K5accc

H3K4me3H3K4me3H3K4me3

H4K8ac-H3K4me

3

H4K8ac-H3K4me

3

H4K8ac-H3K4me

H4K8H4K8H4K8acacac 3

H3K4me3H3K4me3H3K4me3

H4K16

ac-H^3

K4me3

H4K16

ac-H^3

K4me3

H4K16

ac-H^3

H3K4mH4K16acH4K16acH4K16ac K4me3

e3

H3K4m

e3

H3K4m

H4K2 e3

0ac-H3K

4me3

H4K2

0ac-H3K

4me3

H4K2

0ac-H3K

4me3

H4K20acH4K20acH4K20ac

H3K4me

3

H3K4me

3

H3K4me

3

H4KpolyacH4KpolyacH4KpolyacH4Kpolyac-H3K4me3H4Kpolyac-H3K4me3H4Kpolyac-H3K4me3

H3T118HH3T118HH3T118HH4R45AH4R45AH4R45AH4R45A-H3T118HH4R45A-H3T118HH4R45A-H3T118HH3K4me3H3K4me3H3K4me3

3 e

m^9 K

3 H-

ca^5

K^4 H

3 e

m^9 K

3 H-

ca^5

K^4 H

3 e

m^9 K

3 H-

ca^5

K^4 H

H3K9me3H3K9me3H3K9me3H4K5acH4K5acH4K5ac

H4K12ac-H3K9me3H4K12ac-H3K9me3H4K12ac-H3K9me3

H4K

12ac

H4K

12ac

H4K

12ac

H3K9me3H3K9me3H3K9me3

H4K

16ac-

H3K9me3

H4K

16ac-

H3K9me3

H4K

16ac-

H3K9me3H3K9me3H3K9me3H4K16acH4K16acH4K16acH3K9me3

H (^4) K2
0ac-
H (^3) K9m
e 3
H (^4) K2
0ac-
H (^3) K9m
e 3
H (^4) K2
0ac-
H (^3) K9m
e 3
H4K
20ac
H4K
20ac
H4K
H3K9me20ac
3
H3K9me
3
H3K9me
3
H4K
polyac-H3K9me3
H4K
polyac-H3K9me3
H4K
polyac-H3K9me3
H4Kpolya
c
H4Kpolya
c
H4Kpolya
c
HHH (^333) K9me3K9me3K9me3
H4K8ac-H3
K27me3
H4K8ac-H3
K27me3
H4K8ac-H3
H4K27me3
K8a
c
H4K
8ac
H4K
8ac
H3K27
me3
H3K27
me3
H3K27
me3
H4K1
2ac-H3K
(^2) 7me3
H4K1
2ac-H3K
(^2) 7me3
H4K1
2ac-H3K
H4K12a^2 7me3
c
H4K12a
c
H4K12a
c
H3K27
me3
H3K27
me3
H3K27
me3
H4K16
ac-H3K27m
e3
H4K16
ac-H3K27m
e3
H4K16
ac-H3K27m
H4K (^20) ac-H3K27meH3K27me3H3K27me3H3K27me3HHH4K16a4K16a4K16accce3
3
H4K (^20) ac-H3K27me
3
H4K (^20) ac-H3K27me
H3K27meH4K20aH4K20aH4K20accc^3
3
H3K27me
3
H3K27me
3
H4Kpolya
c-H3K27
me3
H4Kpolya
c-H3K27
me3
H4Kpolya
c-H3K27
HHH4Kpolyac4Kpolyac4Kpolyacme3
H3KpolyacH3KH3KH3K27m27m27me3e3e3
H3KpolH3Kpolyacyac-H2BK120u-H2BK120u-H2BK120ubbb
H3KH3KH3Kpolyacpolyacpolyac
H4R45A-H2BKH2BKH2BK120ub120ub120ub
H4R45A-H4R45A-H3R4H3R4H3R42A2A2A
HHH4R45A4R45A4R45A
HHH3R42A3R42A3R42A
H4K8ac-H3K9meH4K8ac-H3K9meH4K8ac-H3K9me^333
H4H4H4K8K8K8aaaccc
HHH3K9m3K9m3K9me3e3e3
H4K5ac-H3K27
me3
H4K5ac-H3K27
me3
H4K5ac-H3K27
me3
H4K5a
c
H4K5a
c
H4K5a
c
H3K2
7me^3
H3K2
7me^3
H3K2
7me^3
H3K
4me3
-H2B
K120
ub
H3K
4me3
-H2B
K120
ub
H3K
4me3
-H2B
K120
ub
H3K4me
3
H3K4me
3
H3K4me
3
H2B
K120ub
H2B
K120ub
H2B
K120ub
H4R17A,R19A-H3T118HH4R17A,R19A-H3T118HH4R17A,R19A-H3T118H
H4R17
A,R19A
H4R17
A,R19A
H4R17
A,R19AH3T118HH3T118HH3T118H
H3K9me3-H
(^2) BK120u
b
H3K9me3-H
(^2) BK120u
b
H3K9me3-H
(^2) BK120u
b
H3K
9me3
H3K
9me3
H3K
9me3
H2BK120
ub
H2BK120
ub
H2BK120
ub
H3K
27me3

• H2BK12
  0ub

H3K

27me3

• H2BK12
  0ub

H3K

27me3

• H2BK12
  0ub

H3K27me3H3K27me3H3K27me3

H2BK

120ub

H2BK

120ub

H2BK

120ub

H4R

17A,R1

9A-H3R42A

H4R

17A,R1

9A-H3R42A

H4R

17A,R1

9A-H3R42A

HHH4R17A,R19A4R17A,R19A4R17A,R19A

H3R42

A

H3R42

A

H3R42

A

H2BK1

(^20) ub-H
(^4) R (^3) me
(^2) a
H2BK1
(^20) ub-H
(^4) R (^3) me
(^2) a
H2BK1
(^20) ub-H
(^4) R (^3) me
(^2) a
H2BK120u
b
H2BK120u
b
H2BK120u
b
H4R3me
2a
H4R3me
2a
H4R3me
2a
H2AK1 (^19) ub
-H4R 3 me 2 a
H2AK1 (^19) ub
-H4R 3 me 2 a
H2AK1 (^19) ub
-H4R 3 me 2 a
HHH 222 AAAK1K1K1 111 9u9u9ubbb
H4RH4RH4R 333 me2me2me2aaa
-3 -2 -1 0 1
(+) (+)--> (++)
(-) (+)--> (+)
(+) (-)--> (-)
(-) (-)--> (--)
cBAF Activity PBAF Activity ncBAF Activity
unmodifiedH4KpolyacunmodifiedH4Kpolyac
0.000
0.005
0.010
0.015
0.020
0.025
kobs (min
-1
)
ncBAF
dBRD9: (-) (-) (+) (+)
MN:
p = 0.000751 p = 0.000690
unmodifiedH4KpolyacunmodifiedH4Kpolyac
0.00
0.01
0.02
0.03
0.04
0.05
kobs (min
-1
)
p = 0.00121
cBAF
dBRD9: (-) (-) (+) (+)
MN:
PBAF
dBRD9: (-) (-) (+) (+)
unmodifiedH4KpolyacunmodifiedH4Kpolyac
MN:
0.000
0.005
0.010
0.015
0.020
0.025
kobs (min
-1
)
p = 0.00241
0.00
0.01
0.02
0.03
0.04
kobs (min
-1
)
PBAF SMARCB1
MN:
p = 0.00942
−3 −2 −1 0 1
ncBAF Activity
−3
−2
−1
0
1
PBAF
PBAF^ SMARCB1
H4Kpolyac-H3K9me3
H4Kpolyac-H3K27me3
H4Kpolyac-H3K4me3
H4Kpolyac-
H3K27me3
H4Kpolyac-H3K9me3
H4Kpolyac-H3K4me3
Cor=0.89
Cor=0.70
Activity (PBAF/PBAF SMARCB1 vs. ncBAF)
H4K16ac-H3K4me3H4Kpolyac-H3K9me3H4K16ac-H3K27me3H4Kpolyac-H3K4me3H4Kpolyac-H3K27me3H4K16ac-H3K9me3H4K12ac-H3K9me3H4K20ac-H3K9me3
H4K12acH4K16ac
H4K12ac-H3K4me3H4K12ac-H3K27me3
H4K20acH4K8ac
H4K8ac-H3K27me3H4K5ac-H3K9me3
H4K77ac
H4K5ac-H3K4me3
H4Kpolyac
H4K20ac-H3K4me3H4K8ac-H3K9me3H4K8ac-H3K4me3
H4K5ac
H4K5ac-H3K27me3
H4K91ac
Mark
−0.5
0.0
0.5
1.0
1.5
Activity Score
PBAF
ncBAF
SMARCB1
Activity (REAA)
H4Kpolyac-H3K9me3H4Kpolyac-H3K4me3H4Kpolyac-H3K27me3
H4KpolyacH4K20ac
H4K20ac-H3K27me3H4K20ac-H3K4me3H4K20ac-H3K9me3H4K12ac-H3K4me3H4K16ac-H3K4me3H4K8ac-H3K4me3H4K16ac-H3K9me3
H4K12ac
H4K8ac-H3K27me3H4K12ac-H3K27me3H4K16ac-H3K27me3H4K5ac-H3K4me3H4K12ac-H3K9me3H4K5ac-H3K27me3
H4K16ac
Mark
0.0
0.5
1.0
1.5
2.0
Binding Score
Binding (Pulldown)
PBAF
ncBAF
SMARCB1
PBAF/ PBAF
SMARCB1 Activity
unmodifiedH4Kpolyac
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