The nucleosome, made up of four core histone proteins (H2A, H2B, H3, and H4), and linker histone H1 are the primary building blocks of chromatin. Originally thought to function as a static scaffold for DNA packaging, histones have more recently been shown to be dynamic proteins, undergoing multiple types of post-translational modifications that regulate chromatin condensation and DNA accessibility. For example, acetylation of lysine residues has long been associated with histone deposition and transcriptional activation, and more recently found to be associated with DNA repair. Phosphorylation of serine and threonine residues facilitates chromatin condensation during mitosis and transcriptional activation of immediate-early genes. Methylation of lysine and arginine residues function as a major determinant for formation of transcriptionally active and inactive regions of chromatin and is crucial for proper programming of the genome during development.
Histone | Site | Histone-modifying Enzymes | Proposed Function | Ref. # |
---|---|---|---|---|
H2A | Lys4 (S. cerevisiae) | Esa1 | transcriptional activation | (1) |
Lys 5 (mammals) | Tip60, p300/CBP | transcriptional activation | (2,3) | |
Lys7 (S. cerevisiae) | Hat1 | unknown | (4) | |
Esa1 | transcriptional activation | (1) | ||
H2B | Lys5 | p300, ATF2 | transcriptional activation | (5,3) |
Lys11 (S. cerevisiae) | Gcn5 | transcriptional activation | (6) | |
Lys12 (mammals) | p300/CBP, ATF2 | transcriptional activation | (5,3) | |
Lys15 (mammals) | p300/CBP, ATF2 | transcriptional activation | (5,3) | |
Lys16 (S. cerevisiae) | Gcn5, Esa1 | transcriptional activation | (6) | |
Lys20 | p300 | transcriptional activation | (3) | |
H3 | Lys4 (S. cerevisiae) | Esa1 | transcriptional activation | (1) |
Hpa2 | unknown | (7) | ||
Lys9 | unknown | histone deposition | (8) | |
Gcn5, SRC-1 | transcriptional activation | (10,9) | ||
Lys14 | unknown | histone deposition | (8) | |
Gcn5, PCAF | transcriptional activation | (11,3) | ||
Esa1, Tip60 | transcriptional activation | (2,1) | ||
DNA repair | (11,12) | |||
SRC-1 | transcriptional activation | (10) | ||
Elp3 | transcriptional activation (elongation) | (13) | ||
Hpa2 | unknown | (7) | ||
hTFIIIC90 | RNA polymerase III transcription | (14) | ||
TAF1 | RNA polymerase II transcription | (15) | ||
Sas2 | euchromatin | (16) | ||
Sas3 | transcriptional activation (elongation) | (17) | ||
p300 | transcriptional activation | (3) | ||
Lys18 | Gcn5 | transcriptional activation, DNA repair | (9) | |
p300/CBP | DNA replication, transcriptional activation | (18,3) | ||
Lys23 | unknown | histone deposition | (8) | |
Gcn5 | transcriptional activation, DNA repair | (9) | ||
Sas3 | transcriptional activation (elongation) | (17) | ||
p300/CBP | transcriptional activation | (18,3) | ||
Lys27 | p300/CBP | transcriptional activation | (93, 94) | |
Lys36 | Gcn5 | transcriptional activation | (82) | |
Lys56 (S. cerevisiae) | Spt10 | transcriptional activation | (19) | |
DNA repair | (20) | |||
H4 | Lys5 | Hat1 | histone deposition | (21) |
Esa1, Tip60 | transcriptional activation | (2,1) | ||
DNA repair | (11,12) | |||
ATF2 | transcriptional activation | (5) | ||
Hpa2 | unknown | (7) | ||
p300 | transcriptional activation | (3) | ||
Lys8 | Gcn5, PCAF | transcriptional activation | (22,3) | |
Esa1, Tip60 | transcriptional activation | (2,1) | ||
DNA repair | (11,12) | |||
ATF2 | transcriptional activation | (5) | ||
Elp3 | transcriptional activation (elongation) | (13) | ||
p300 | transcriptional activation | (3) | ||
Lys12 | Hat1 | histone deposition | (21) | |
telomeric silencing | (23) | |||
Esa1, Tip60 | transcriptional activation | (2,1) | ||
DNA repair | (11,12) | |||
Hpa2 | unknown | (7) | ||
p300 | transcriptional activation | (3) | ||
Lys16 | Gcn15 | transcriptional activation | (22) | |
MOF (D. melanogaster) | transcriptional activation | (24) | ||
Esa1, Tip60 | transcriptional activation | (2,1) | ||
DNA repair | (11,12) | |||
ATF2 | transcriptional activation | (5) | ||
Sas2 | euchromatin | (6,2) | ||
Lys91 (S. cerevisiae) | Hat1/Hat2 | chromatin assembly | (25) |
Histone | Site | Histone-modifying Enzymes | Proposed Function | Ref. # |
---|---|---|---|---|
H1 | Lys26 | Ezh2 | transcriptional silencing | (48, 49) |
H2A | Arg3 | PRMT1/6, PRMT5/7 | transcriptional activation, transcriptional repression | (83) |
H3 | Arg2 | PRMT5, PRMT6 | transcriptional repression | (83) |
Arg8 | PRMT5, PRMT2/6 | transcriptional activation, transcriptional repression | (31, 88) | |
Arg17 | CARM1 | transcriptional activation | (18) | |
Arg26 | CARM1 | transcriptional activation | (83) | |
Arg42 | CARM1 | transcriptional activation | (89) | |
Lys4 | Set1 (S. cerevisiae) | permissive euchromatin (di-Me) | (26) | |
Set 7/9 (vertebrates) | transcriptional activation (tri-Me) | (27) | ||
MLL, ALL-1 | transcriptional activation | (28, 29) | ||
Ash1 (D. melanogaster) | transcriptional activation | (30) | ||
Lys9 | Suv39h, Clr4 | transcriptional silencing (tri-Me) | (32, 33) | |
G9a | transcriptional repression genomic imprinting | (34) | ||
SETDB1 | transcriptional repression (tri-Me) | (35) | ||
Dim-5 (N. crassa), Kryptonite (A. thaliana) | DNA methylation (tri-Me) | (36, 37) | ||
Ash1 (D. melanogaster) | transcriptional activation | (30) | ||
Lys27 | Ezh2 | transcriptional silencing | (38) | |
X inactivation (tri-Me) | ||||
G9a | transcriptional silencing | (34) | ||
Lys36 | Set2 | transcriptional activation (elongation) | (39) | |
Lys79 | Dot1 | euchromatin | (40) | |
transcriptional activation (elongation) | (41) | |||
checkpoint response | (42) | |||
H4 | Arg3 | PRMT1/6 | transcriptional activation | (43) |
PRMT5/7 | transcriptional repression | (31) | ||
Lys20 | PR-Set7 | transcriptional silencing (mono-Me) | (44) | |
Suv4-20h | heterochromatin (tri-Me) | (45) | ||
Ash1 (D. melanogaster) | transcriptional activation | (30) | ||
Set9 (S. pombe) | checkpoint response | (46) | ||
Lys59 | unknown | transcriptional silencing | (47) |
Histone | Site | Histone-modifying Enzymes | Proposed Function | Ref. # |
---|---|---|---|---|
H1 | Ser27 | unknown | transcriptional activation, chromatin decondensation | (48,49) |
H2A | Ser1 | unknown | mitosis, chromatin assembly | (50) |
MSK1 | transcriptional repression | (51) | ||
Ser122 (S. cerevisiae) | unknown | DNA repair | (53) | |
Ser129 (S. cerevisiae) | Mec1, Tel1 | DNA repair | (54,55) | |
Ser139 (mammalian H2A.X) | ATR, ATM, DNA-PK | DNA repair | (56-58) | |
Thr119 (D. melanogaster) | NHK1 | mitosis | (52) | |
Thr120 (mammals) | Bub1, VprBP | mitosis, transcriptional repression | (90,91) | |
Thr142 (mammalian H2A.X) | WSTF | apoptosis, DNA repair | (92) | |
H2B | Ser10 (S. cerevisiae) | Ste20 | apoptosis | (59) |
Ser14 (vertebrates) | Mst1 | apoptosis | (60) | |
unknown | DNA repair | (61) | ||
Ser33 (D. melanogaster) | TAF1 | transcriptional activation | (62) | |
Ser36 | AMPK | transcriptional activation | (84) | |
H3 | Ser10 | Aurora-B kinase | mitosis, meiosis | (64,65) |
MSK1, MSK2 | immediate-early gene activation | (66) | ||
IKK-α | transcriptional activation | (67) | ||
Snf1 | transcriptional activation | (68) | ||
Ser28 (mammals) | Aurora-B kinase | mitosis | (70) | |
MSK1, MSK2 | immediate-early activation | (66,71) | ||
Thr3 | Haspin/Gsg2 | mitosis | (63) | |
Thr6 | PKCβI | (85) | ||
Thr11 (mammals) | Dlk/Zip | mitosis | (69) | |
Tyr41 | JAK2 | transcriptional activation | (86) | |
Tyr45 | PKCδ | apoptosis | (87) | |
H4 | unknown | mitosis, chromatin assembly | (50) | |
Ser1 | CK2 | DNA repair | (71) |
Histone | Site | Histone-modifying Enzymes | Proposed Function | Ref. # |
---|---|---|---|---|
H2A | Lys119 (mammals) | Ring2 | spermatogenesis | (73) |
H2B | Lys120 (mammals) | UbcH6 | meiosis | (74) |
Lys123 (S. cerevisiae) | Rad6 | transcriptional activation | (75) | |
euchromatin |
Histone | Site | Histone-modifying Enzymes | Proposed Function | Ref. # |
---|---|---|---|---|
H2A | Lys126 (S. cerevisiae) | Ubc9 | transcriptional repression | (76) |
H2B | Lys6 or Lys7 (S. cerevisiae) | Ubc9 | transcriptional repression | (76) |
H4 | N-terminal tail (S. cerevisiae) | Ubc9 | transcriptional repression | (77) |
Histone | Site | Histone-modifying Enzymes | Proposed Function | Ref. # |
---|---|---|---|---|
H2A | Lys9 | biotinidase | unknown | (78) |
Lys13 | biotinidase | unknown | (78) | |
H3 | Lys4 | biotinidase | gene expression | (79) |
Lys9 | biotinidase | gene expression | (79) | |
Lys18 | biotinidase | gene expression | (79) | |
H4 | Lys12 | biotinidase | DNA damage response | (80,81) |
CST would like to thank Prof. Craig Peterson, University of Massachusetts Medical School, Worcester, Massachusetts, for reviewing this table.
created May 2007
revised March 2018