Science - USA (2021-07-16)

308 16 JULY 2021•VOL 373 ISSUE 6552 sciencemag.org SCIENCE

complex activity on unmodified (wild-type) mononucleosomes is shown as a black
line; mononuclesomes showing complex activity > 2 SD from WT are shown in red,
< 2 SD from WT are shown in blue, and the remainder are shown in gray. See
methods in the supplementary materials for additional information. (E) Proportion of

the unchanged and statistically significant positive and negative regulators of binding

and activity measurements across cBAF, PBAF, and ncBAF complexes. Positive

and negative marks identified as those greater than ±2 SD from the unmodified

average. See methods for additional information.

D

−3 −2 −1 0 1

cBAF Remodeling Activity

−2

−1

0

1

2

3

4

H3Kpolyac

(H2A+H2B+H3)KpolyacH3Y41phH3Kpolyac-

H2Bub

(H3+H4)Kac H3K14cr

H3K14ac

(H2A+H2B+H3+H4)Kpolyac

H4R45A-H3R42A

Acidic patch H2BK116ac

H3K4me3-H2BK120ub

cBAF Binding vs. Activity

−3 −2 −1 0 1

PBAF Remodeling Activity

−2

−1

0

1

2

PBAF Binding

(H2A+H2B+H3+H4)Kpolyac

(H2A+H2B+H3)Kpolyac

H3K14ac

H3K18acK23ac

H3Kpolyac

H3Kpolyac

-H2Bub

H3Y41ph

(H3+H4)Kpolyac

H4R45A-

H3R42A

Acidic patch

H2BKpolyac

PBAF Binding vs. Activity

−3 −2 −1 0 1

ncBAF Remodeling Activity

−0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

ncBAF Binding

(H2A+H2B+H3+H4)Kpolyac

(H2A+H2B+H3)Kpolyac

H3K14ac

H3Kpolyac

H3Kpolyac-H2Bub

H3Y41ph

H4Kpolyac-H3K27me3

H4Kpolyac-H3K4me3

(H3+H4)Kpolyac

H4Kpolyac-H3K9me3

H4R17A,R19A-H3R42A

H3R42A

Acidic patch

ncBAF Binding vs. Activity

PCC=0.648 PCC=0.765 PCC=0.432

ABH3 tail acetylation (all complexes) C

H3 tail trimethylation (all complexes)

acidic patch

H2AK119ubH4R45A H3Y41ph

H4R17AR19A H2BK120ub

-1.3 0 0.7

Remodeling activity

E56A

E61A

E64A

D90A

E91A

E92A

E113A

E105A

H3K9

H3K14

H3K18

H3K23

H3K27 H3K4

H3R2

H3K4

H3K9

H3K27

H3K36

-1.1 0 1.1

Remodeling activity

H4K5 H4K8

H4K12

H4K20

H4K16

H4K5 H4K8

H4K12

H4K20

H4K16

-0.54 0 0.54

Remodeling activity

H4 tail acetylation (cBAF/PBAF)

H4 tail acetylation (ncBAF)

cBAF

UnmodifiedH4R45AH4R17AR19AH2AK11

9ub

H2BK120ubH3K14ac

H3K14crH3K27acH3K4me1H3K4me3H3K9me3H3K27me3

H3K4me3K27me3

H4Kpolyac

H3K4me3-H4KpolyacH3K9me3-H4Kpolyac

0

50

100

150

200

relative rate (%)

ncBAF

UnmodifiedH4R45AH4R17AR19AH2AK

119ub

H2BK120ubH3K14ac

H3K14crH3K27acH3K4me1H3K4me3H3K9me3H3K27me3

H3K4me3K27me3

H4Kpolyac

H3K4me3-H4KpolyacH3K9me3-H4Kpolyac

0

50

100

150

200

relative rate (%)

UnmodifiedH4R45AH4R17AR19AH2AK119ubH2BK120ubH3K14acH3K14crH3K27acH3K4me1H3K4me3H3K9me3H3K27me3

H3K4me3K27me3

H4Kpolyac

H3K4me3-H4KpolyacH3K9me3-H4Kpolyac

0

50

100

150

200

PBAF

relative rate (%)

E

Fig. 2. Histone modification hotspots affect mSWI/SNF family complex
nucleosome remodeling activities.(A) Modifications of all key residues in the
acidic patch (H2AE56A, H2AE61A, H2AE64A, H2AD90A, H2AE91A, H2AE92A,
H2BE105A, and H2BE113A), the H4 tail basic patch (H4R17A, R19A), and
H2AK119ub uniformly inhibit the remodeling activities of all three complex types
(blue), whereas modifications mapping to histone-DNA interfaces (H3Y41ph and

the H4R45A Sin- mutant) promote the remodeling activity (red). All sites are

colored according to the average of log 2 (fold change versus the unmodified

nucleosome) values of the three complexes. Note that acidic patch sites have an

average log 2 value of−2.9, which is out of the color bar range and is colored

blue. Single-letter abbreviations for the amino acid residues are as follows:

A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu;

RESEARCH | RESEARCH ARTICLES