See online version for for legend and references.458 Cell 159, October 9, 2014 ©2014 Elsevier Inc. DOI http://dx.doi.org/10.1016/j.cell.2014.09.037

Snap

Shot:

His

tone M

odifi c

atio

ns

He

Hua

ng,1

Ben

jam

in R

. Sab

ari,2

Ben

jam

in A

. Gar

cia,

3 C

. Dav

id A

llis,

2 an

d Y

ing

min

g Z

hao

1

1 Ben

May

Dep

artm

ent

of

Can

cer

Res

earc

h, T

he U

nive

rsity

of

Chi

cag

o, C

hica

go

, IL

6063

7, U

SA

2 Lab

ora

tory

of

Chr

om

atin

Bio

log

y an

d E

pig

enet

ics,

The

Ro

ckef

elle

r U

nive

rsity

, New

Yo

rk, N

Y 1

0021

, US

A3 D

epar

tmen

t o

f B

ioch

emis

try

and

Bio

phy

sics

, Uni

vers

ity o

f P

enns

ylva

nia,

Phi

lad

elp

hia,

PA

191

04, U

SA

Bo

xes

ind

icat

e g

lob

ular

do

mai

n

Me

Ac

Pr

Bu

Cr

Hib

Ma

Su

Ub

Fo

Cit

Ph

OH

Og

Ar

Met

hyla

tio

n (K

, R)

Ace

tyla

tio

n (K

, S, T

)P

rop

iony

lati

on

(K)

But

yryl

atio

n (K

)C

roto

nyla

tio

n (K

)2-

Hyd

roxy

iso

but

yryl

atio

n (K

)M

alo

nyla

tio

n (K

)S

ucci

nyla

tio

n (K

)

Ub

iqui

tinat

ion

(K)

Fo

rmyl

atio

n (K

)

Cit

rulli

nati

on

(R)

Pho

spho

ryla

tio

n (S

, T, Y

, H)

Hyd

roxy

lati

on

(Y)

O-G

lcN

Acy

latio

n (S

, T)

AD

P r

ibo

syla

tion

(K, E

)

H3

10

20

30

40

55

6

2

7

8

80

1

06

1

14

121

12

7

1

30

+ H3N

-AQ

AG

GA

PQ

LAA

AA

PA

GG

VP

HP

GV

…Q

T… I

L…F

DL

FQS

S…

DN

…A

R…

PD

…A

RIR

G E

RA

-CO

O-

Ph

Me

Cit

Ph

Me

Ac

Cr

Hib

Ph

Me

Cit

Me

Ac

Bu

Cr

Hib

Ac

Ph

Og

Me/

Ac/

Bu

Hib

/Su/

Ub

Me

Cit

Me/

Ac/

Bu/

Cr

Hib

/U

b/

Fo

Ac

Me/

Ac/

Pr/

Bu/

Cr

Hib

/Su/

Ub

/Fo

Me

Cit

Ac

Ph

Me

Ac

Hib

Ub

Me

Ac

Ar

Me

Ph

Me

Ph

Ph

Me/

Ac/

Pr/

Cr/

Hib

Su/

Ma/

Ub

/Fo

Me

Me

Ac

Hib

Fo

Me/

Ac/

Bu/

Cr

Hib

/Su/

Ub/

Ar

Ac

Ph

Me

Ph

Ph

Ac

Bu

Me/

Ac/

Bu/

Cr

Hib

/Su/

Fo/U

b

Me

Og

Me/

Ac/

Bu/

Cr

Hib

/Su/

Ub

/Fo

H4

Me

Cit

Ph

Me

CitMe/

Ac/

Pr

Bu/

Cr/

Hib

Ac/

Pr/

Bu

Cr/

Hib

Me/

Ac/

Pr/

Bu

Cr/

Hib

/Su/

FoM

e/A

c/P

r/B

uC

r/H

ib/A

r

Me

Cit

Me

Ac

Me

Me/

Ac/

Pr/

Bu

Hib

/Su/

Ub

/Fo

Me

Pr

Bu

Hib

Ph

Og

Ph

OH

Me

Me

Cr

Hib

Ub

FoM

eM

eM

e

Me/

Ac/

Pr/

Bu/

Cr

Hib

/Su/

Ub

/Fo

Me/

Ac/

Pr/

Bu

Hib

/Su/

Fo

Ph

OH

Ac/

Pr/

Bu/

Cr

Hib

/Su/

Ub

/Fo

Ph

Ph

Ph

AcH

N-

GG

GG

GLG

GG

AV

LD

NI

QG

ITP

AI

R…

VR

IG

LIE

ET

GV

LV

…V

ID

AV

TYTE

ATV

TAM

DV

VA

LS

RK

KK

KR

HR

KR

KR

KS

YR

KR

HK

RK

YK

RQ

G R

TLY

GFG

G-C

OO

-

10

2

0

30

43

5

0

60

65

70

80

9

0

100

H2A AcH

N-S

GR

GK

QG

GK

AR

AK

AK

TRS

SR

AG

LQ

FP

VG

RV

HR

LLR

KG

NY

AE

RV

...P

VY

L…LT

A…

AR

DN

KK

T…

IRN

DE

ELN

KLL

GK

VT

I…LL

PK

KT

ES

HH

KAK

GK

-CO

O-

10

2

0

3

0

40

48

5

0

58

70

8

7

9

0

60

1

00

115

120

Ph

Me

Cit

Ac

Bu

Hib

Me

Ac

Hib

Su

Me

Ac

Ub

Ar

Ac

Ub

Me

Ac/

Cr/

Hib

Su/

Ub

/Fo

OH

Me

Ph

Ph

Me

Me

Ac

Hib

Hib

Me

Me/

Ac/

Pr/

Bu/

Cr

Hib

/Su/

Ub

/Fo

Me

Ph

Og

Cr

Ub

Ph

Me/

Ac/

Cr

Hib

/U

b/

FoP

h

Me

Pr

Cr

Ub

Ac

Ac

H2B

+ H3N

-PE

PA

KS

A…

PK

KG

SK

KA

VT

KA

QK

KD

…R

KR

SR

KE

SY

S…

YK

VLK

...T

GIS

SK

...S

...S

EA

SR

LAH

YN

KR

ST

ITS

RE

…VR

L…

AK

H…

GT

KA

VT

KY

TSA

K-C

OO

-

10

20

29

30

42

52

64

75

8

0

90

9

8

107

11

4

120

100

Ar

Ph

Ph

Ac

Ar

Ph

OH

Ph

Ph

Ph

Ph

Me

OH

Me

Ph

Ph

Ph

Me

Me

Ph

Ph

Ac

Me/

Ac/

Bu/

Cr

Hib

/Su/

FoA

cB

uC

r

Me

Ac

Bu

Cr

Hib

Me

Ac

Bu

Cr

Ac

Bu

Cr

Me/

Ac/

Bu

Cr/

Hib

/Ub

Me

Ac

Bu

Cr

Hib

Ac

Hib

Me/

Cr/

Hib

Su/

Ub

/Fo

Ph

Og

Me

Ac

Hib

Su

Fo

Me/

Ac/

Bu/

Hib

Su/

Ub

/Fo

Me

Ac

Hib

Ub

Me

Ac

Hib

Su

Me/

Ac/

Cr/

Hib

Su/

Ub

/Fo

Me/

Ac/

Cr/

Hib

Ma/

Su/

Ub

/Fo

Ac

Hib

Su

Ub

Fo

Ph

Ac

Me

Ub

Hib

Ph

Ph

Ph

Ph

Me

Ac

Hib

Me

Hib

Ub

Hib

Ub

Hib

Su

Me

Hib

Ub

FoM

eH

ibC

rH

ibU

bFo

Me/

Ac/

Cr

Hib

/Ub

Me

Ac

H1

+ H3N

-SE

TA

...E

KA

PV

KK

KA

AK

KA

GG

TPR

KA

SG

PP

VS

ELI

TK

AV

AA

SK

ER

SG

VS

LAA

LK

KA

L...G

YD

VE

KN

NS

RIK

LGLK

SLV

SK

GTL

VQ

TK

GTG

AS

GS

FK

LNK

- CO

O-K

KK

P…

AK

AA

SK

A…

PK

TV

KA

KK

PS

KA

VK

KTV

TA

AA

PK

KA

…S

KK

PT

A…

AK

KP

KK

AA

GV

PK

KPK

TGG

AK

KVK

PK

AE

GS

AA

K

15

2

0

30

40

50

6

0

69

70

80

90

100

209

190

185

180

17

0

160

15

7

144

1

40

13

0

120

110

Ar

Ph

Hib

Ph

Ac

Ph

Ph

Me

Ac

FoM

eA

c

Me

Ac

Hib

Me

Hib

Me/

Ac/

Cr/

Hib

Su/

Ub

/Fo

Ac

Ph

Ac/

Hib

/Su

Ub

/Fo

Me

Ac

Hib

Ub

Me/

Ac/

Hib

Su/

Fo

Me/

Ac/

Cr/

Hib

Su/

Ub

/Fo

Ph

OH

Ac

Hib

Ub

FoH

ibFo

Ac/

Cr/

Hib

Su/

FoM

e/A

c/C

r/H

ibS

u/U

b/

FoM

e /A

c/C

r/H

ibS

u/U

b/

Fo

Me

Ac

Su

Ub

Cit

HN

H

O

HN

O

HN

O

HN

O

HN

O

HN

O

HN

O

HN

O

HN

O

OH

O

OO

OU

biq

uit

in

H2N

H NN

NH

HN

NH

2

NH

NN

H2

NH

HN

NH

NH

H2N

O

OPO

OO

OH

OH

O

O

O Ac H

NO

H

OH

OH

OP

OO

H

OP

OO

H

O

OO

OH

OH

OH

OH

N/ O

N

NN N

NH

2

NN

P OOO

NN

P OOO

++

+

++

+

+

--

- -

---

-

-

Po

siti

ve c

hang

e

Neg

ativ

e ch

arg

e

KFo

KA

c

KP

r

KB

u

KC

rK

Hib

KM

a

K

Su

KU

b

K

Me

S/T

Ac

RM

e

R

Cit

S

/T/Y

Ph

HP

h

Y

OH

S/T

Og

K/E

Ar

RT

KT

RK

ST

KR

KT

KR

KS

TK

KR

YR

TK

SR

KK

TR

TK

KR

SnapShot: Histone ModificationsHe Huang,1 Benjamin R. Sabari,2 Benjamin A. Garcia,3 C. David Allis,2 and Yingming Zhao1

1Ben May Department of Cancer Research, The University of Chicago, Chicago, IL 60637, USA2Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10021, USA3Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA

The histone proteins are decorated by a variety of protein posttranslational modifications (also called histone marks). Histone marks are critical to dynamic modulation of chro-matin structure and function, contributing to the cellular gene expression program. In addition to the well-studied acetylation and methylation modifications, recent studies have revealed several new types of histone marks, including lysine propionylation, lysine butyrylation, lysine crotonylation, lysine 2-hydroxyisobutyrylation, lysine malonylation, and lysine succinylation. Preliminary studies on some of the new histone marks (e.g., crotonylation and 2-hydroxyisobutyrylation) suggest that their effects on chromatin function are distinct from those of lysine acetylation. Given that the newly discovered lysine acylation reactions likely use the corresponding acyl-CoA molecules as cofactors, it is proposed that histone acylations provide a link between cellular metabolism and epigenetic mechanisms.

This SnapShot summarizes the reported human, mouse, and rat histone marks, including recently identified lysine acylation marks.

Acknowledgments

This work was funded by institutional support from The Rockefeller University to C.D.A.; by NIH grants GM105933, CA160036, and RR020839 to Y.Z.; and by DP2OD007447 to B.A.G.

RefeRences

Arnaudo, A.M., and Garcia, B.A. (2013). Epigenet. Chromatin 6, 24.

Beck, H.C., Nielsen, E.C., Matthiesen, R., Jensen, L.H., Sehested, M., Finn, P., Grauslund, M., Hansen, A.M., and Jensen, O.N. (2006). Mol. Cell. Proteomics 5, 1314–1325.

Chen, Y., Sprung, R., Tang, Y., Ball, H., Sangras, B., Kim, S.C., Falck, J.R., Peng, J., Gu, W., and Zhao, Y. (2007). Mol. Cell. Proteomics 6, 812–819.

Dai, L., Peng, C., Montellier, E., Lu, Z., Chen, Y., Ishii, H., Debernardi, A., Buchou, T., Rousseaux, S., Jin, F., et al. (2014). Nat. Chem. Biol. 10, 365–370.

Fierz, B., and Muir, T.W. (2012). Nat. Chem. Biol. 8, 417–427.

Jenuwein, T., and Allis, C.D. (2001). Science 293, 1074–1080.

Kouzarides, T. (2007). Cell 128, 693–705.

Tan, M., Luo, H., Lee, S., Jin, F., Yang, J.S., Montellier, E., Buchou, T., Cheng, Z., Rousseaux, S., Rajagopal, N., et al. (2011). Cell 146, 1016–1028.

Xie, Z., Dai, J., Dai, L., Tan, M., Cheng, Z., Wu, Y., Boeke, J.D., and Zhao, Y. (2012). Mol. Cell. Proteomics 11, 100–107.

Young, N.L., Dimaggio, P.A., and Garcia, B.A. (2010). Cell. Mol. Life Sci. 67, 3983–4000.

458.e1 Cell 159, October 9, 2014 ©2014 Elsevier Inc. DOI http://dx.doi.org/10.1016/j.cell.2014.09.037