Science - USA (2021-07-16)

(Antfer) #1

312 16 JULY 2021•VOL 373 ISSUE 6552 sciencemag.org SCIENCE


DPF2 ARID1
SMARCE1

SMARCD1/2

SMARCC1/SMARCC2

SMARCB1
DPF2 dPHD domain

cBAF complete core module
ATPase

SMARCE1

SMARCD1/2

SMARCC1/SMARCC2

SMARCB1

cBAF core

SMARCE1

SMARCC1/SMARCC2

SMARCB1

cBAF core

SMARCD1

SMARCC1/SMARCC2

SMARCB1

cBAF core

Purified core and ATPase modules

DPF
Nucleosome acidic patch

DPF2 ARID1

ACTL6

ACTB

SMARCE1

SMARCD1/2

SMARCC1/SMARCC2

Bcl7

SMARCA4/2ATPase subunits

SMARCB1

SS18

SMARCA4ATPase helicase region

SMARCA4FL ATPase

SMARCA4Bromo domain

SS18

ACTL6

ACTB
Bcl7

SMARCA4/2Bomo domainSMARCA4/2ATPase subunits

SMARCA4 helicase
AA 537-1393
SMARCA4 FL

ATPase module

A D

E

F

B

C

-2-1 (^01234) H4K8acH4K16ac
H4K5acH4K20ac
H4KpolyacH4K12ac
H4K79a
H4K77aH4K91acc
HH33K27crH3S1Y41ph 0 phc
H3K4
H3K23H3KH3K264ac7acac
ac
HH3K9cr
H3H3K115acH3K36ac3K18ac
K1
8 cr
H3K1
2 2ac
H3K
18 a
cK
23 ac
H3H3K9ac
K^3
7 ac
H3K
56ac
H3K14
ac
H3K1
4 cr
(H2A+
H2B
+H
3)Kpolyac
H3Kp
oly
H3K4ac
me3
H3R2
me
H3K
(^4) m
e1
H3K4m
e (^3) K
(^27)
me3
H3K4me
2
H3K
(^27) m
e 3
H3
H3R2me2K9me3
a
H3K36
me3
H (^3) R42me
2a
H4Kpolyac-H3K4me3
H4K12ac-H3K4me3
H4K
5ac-H
3K4me
3
H4K16ac-
H3K
4me3
H4Kpolyac-H3K27m
e3
H4Kp
olyac-H3
K9me3
H4K20ac-H3K27me3H4K8ac-H3K9me3
H4K20ac-H3K9me3
H4K5ac-H3K27me3
H4K16ac-H
H4K20ac-H3K43K27me 3
H4K5ac-H3K9me3me3
H4K8ac-H3K4me3
H4K16ac-H3K9me3
H4K8ac-H3K27me3
H4K12ac-H3K9me3
H4K^1 2ac-H3K27me3
H3K4me3-H2BK120ub
H3K27me3-H2
BK120ub
H3K9me3-H2
BK120ub
H2BK120ub-H4R3me2a
H2AK119ub-H4R3me2a
H2BK120ubH2AK11
9ub
H^3 Kpolyac-H2BK
1 20ub
(H2A+H2B+H3+
H^4 )Kpolyac
(H3+H4)Kpolyac
H4R17A,
R19A-H3T118HH4R
17 A
,R1
9A
Acidic
patch
H4
R17
A,R
19A-H3
R4^2
A
H3.3K27M
H4R
4 5A-H3
T^11
8 H
H3
.3G
3 4W
H3
.3G3
4 R
H3T118HH3.3G
34V
H4R45AH 3 .3K36MH3
R^4
2A
H4
R45
A-H3R4
2A
H2BK1
1ac
H2
AKp
olyac
H2AK13acH2
AK
(^1) 5a
c
H2AK118
ac
H 2
BK
(^10)
(^8) ac
H2A
K9ac
H2BKpol
yac
H2AK5acH (^2) BK1
25ac
H2B
K15
ac
H (^2) B
K 12
ac
H2B
K120ac
H2BK20acH2BK5ac
H2H2A.ZBK116ac
H2A.Z H3.3H3.3
H2H2BS112GlcNA.X
Ac
5-meCpGH4R3me2s
H4R3me2aH4R3me
H4 acetylation &
H3 acetylation
H4 acetylation &
H3 methylation
H3
methylation
Ubiquitination
H2A/H2B
acetylation
Histone core
& tail mutations
Histone
variants
H4
acetylation
H3 acylation
H4
methylation
Other
H3
phosphorylation
−10 −5 0 5 10
PC1: 35.92%
−6
−4
−2
0
2
4
6
8
10
PC2: 18.42%
ACF
CHRAC
NoRC
NURF46
RSF
SNF2h
WICH
CHD4
cBAF
PBAF
ncBAF
ATPase
Remodeling activities of CRCs: PC1 vs PC2
cBAF complex
-3 -2 -1 (^01) H3K4me3-H2BK120ubH2AK^119 ub-H4R3me2
H2BK120u a
H3K27mb-H 4 R3me^2 a
H2AK119ube3-H2BK120ub
H2BK120ubH3K9me3-H2BK120ub
H3Kpolyac-H
2BK120ub
H3K27H3K4ac
H3K27acH3K122acH3K64accr
H3K
H3K323ac
6ac
H3
K^1
8acK23
ac
HH3K18ac
3K1
8cr
(H2A
+H2
B+H3)
Kpo
lya
c
H3K37
ac
H3K5H3K9crH3K115ac
6 a
c
H3
K9
ac
H3K
14cr
K1H33KpolyacH
ca 4
H4Kpoly
ac-
H3K
4me
3
H4K
12ac
-H3
K4me3
H4Kp
olyac
-H3K27
me3
H4K5a
c-H
(^3) K 4
me3
H4Kpol
yac-H
(^3) K9
me3
H4K
H4K5ac-H3K27me316ac-H3K4me3
H4K20ac-H3K27me3
H4K8ac-H
3K4m
e3
H4K8
H4K20ac-H3K9me3ac-H3K9me3
H4K20ac-H3K4me3
H4K12ac-H3
H 4 K 8 K^27 me3
ac-H3K27me 3
H4K12ac-H3K9me 3
H4K16ac-H^3 K^2 7me3
H4K5ac-H3K^9 me3
H4K16ac-H3K9m
e 3
(H^2 A+H2B+H3+H4)
Kpolyac
(H^3 +H^4
)Kpolyac
H3K4me3K27me3H^3 R2
me
H3R2m
e2a
H3K4me
3
H3K4m
e^2
H3K4m
e^1
H3K9me3
H3K
27 me
3
H3R42me
2 a
H3K3
6me
3
H4R3me2sH4R3me2aH4R3me
4K7H
c9a
H4
Kp
lyao
c
H4K16a
c
H4K20acH4K5a
c
H4
K 1
2ac
H4K
(^7) 7a
c
H 4
K9 1
ac
H4K8
ac
H4R1
(^7) A,
R19
A-H
(^3) T118H
Acidi
c p
atch
H4R17
A,R
19A-H3R42A
H4R17A,
R19
A
H3R
(^4) 2A
H4R45A-H3
T118H
H3T118
H
H (^3) .3
G34V
H3.3K36
M
H3. (^3) K27M
H4R45A



  • H3R42A


HH4R4 (^3) .3G345AW
H3.3G34R
SMARCA4 helicase Activity
SMARCA4 FL Activity
ATPase Activity
cBAF Activity
Ubiquitination
H3 acylation
H4 acetylation and
H3 methylation
H3 methylation
H4 acetylation
Histone core and
tail mutations
H4 methylation
H4 acetylation &
H3 acetylation
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
Binding Score
H3K14ac H3K14cr H3K9ac H3K9cr
Binding of Full and Partial Complexes Across Selected
Acetylated/Crotonylated Marks
Correlation0.4
0.6
0.8
1.0
cBAF core
cBAF core
cBAF core
ATPase
module
cBAF
complex
(complete core
module)
ARID1
SMARCD1/2/3
SMARCE1
ARID1
SMARCD1/2/3
ATPase
cBAF cor
e
SMARCE1
cBA
F core
ARID1cBAF co
re
SMARCD
ATPasemodule cBAF
complex
ATPase
SMARCE1
Complex Module
cBAFPBAFncBAF
ATPaseATPase
cBAFPBAFncBAF
ATPase
cBAFPBAFncBAF
ATPase
cBAFPBAFncBAF
ATPase ATPase ATPaseATPase
SMARCD Binding
SMARCE1 Binding
ARID Binding
ATPase Binding
cBAF Complex Binding
RESEARCH | RESEARCH ARTICLES

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