histone modification

[ HIDE DETAILS ]

DESCRIPTION:

Genomic DNA and HISTONES form a highly condensed structure known as CHROMATIN. Cellular processes that unwind the double helix, such as transcription, replication and DNA repair, have to overcome this natural barrier to DNA accessibility.

Histones are central players for all chromatin-mediated processes processes including transcription, replication and repair. Two of each of the four core histones (H3, H4, H2A and H2B) are forming the nucleosomal core particle around which 147 bp of DNA are wrapped.  The fifth histone, histone H1, binds to the surface of the nucleosomal core particle and stabilises higher order chromatin structure. Histones tails protrude from the nucleosome structure and are subject to several covalent modifications. It has been suggested that these modifications constitute a "histone code". According to this "code" hypothesis this modification pattern is read by proteins, which specifically recognise distinct modifications and then regulate chromatin dynamics and genome function. While it is still under discussion if these modifications form a true "code", it is now well established that changes of histone modifications are involved in the regulation of many - if not all - genes in eukaryotic cells and control complex processes such as development or diseases like cancer.

The covalent modification of histone tails has emerged as a crucial step in controlling the eucaryotic genomes. Eucaryotic cells must possess mechanisms for condensing and decondensing chromatin. Moreover, chromatin condensation is particularly evident during mitosis and apoptotic cell death, whereas chromatin relaxation is necessary for replication, repair, recombination and transcription.
The post-translational modifications of histone tails such as reversible acetylation, phosphorylation and methylation play a critical role in dynamic condensation/relaxation that occurs during the cell cycle. Histone phosphorylation is believed to play a direct role in mitosis, cell death, repair, replication and recombination.

Histone modifying enzymes have been found to be rearranged, mutated or deleted in cancer cells. Therefore, enhancing our understanding of histone modifications will have a powerful impact on the identification of new therapeutic targets and diagnostic markers for the treatment of diseases in which epigenetic states have become distorted or overridden. The set of characterised histone modifications is far from complete. Deciphering their functions represents a key-challenge in biology.

HATs (histone acetyltransferases)
HAT complexes
HDACs (histone deacetylases)
HMTs (histone methyltransferases)
Histone demethylases
Polycomb group proteins
Sir proteins

EXTERNAL DATABASES:
HHMD Human Histone Modification Database
NHGRI Histone Database
MethyCancer database of human DNA Methylation and Cancer

RELATED DISEASES:


Filter
ORTHOLOGY CLASS Homo sapiens L. (human) [HSA] Mus musculus L. (mouse) [MMU] Caenorhabditis elegans Maupas (nematode) [CEL] Drosophila melanogaster Meigen (fruit fly) [DME] Saccharomyces cerevisiae Meyen ex E.C. Hansen (budding yeast) [SCE] Schizo-saccharomyces pombe Lindner (fission yeast) [SPO] Escherichia coli Migula (bacterium) K-12 MG1655 [ECO] Arabidopsis thaliana (L.) Heynh. (mouse-ear cress) [ATH]
ko:K11123 (regulatory protein SIR4) SIR4
ko:K11122 (regulatory protein SIR3) SIR3
ko:K11121 (NAD-dependent histone deacetylase SIR2 [EC:3.5.1.-]) SIR2
HST2
HST1
hst2
sir2
ko:K11120 (regulatory protein SIR1) SIR1
ko:K11450 (lysine-specific histone demethylase 1 [EC:1.-.-.-]) KDM1A Kdm1a spr-5
lsd-1
Su(var)3-3 LDL2
LDL1
FLD
ko:K11446 (histone demethylase JARID1 [EC:1.14.11.-]) KDM5B
KDM5A
KDM5C
KDM5D
Kdm5c
Kdm5d
Kdm5a
Kdm5b
rbr-2 lid
ko:K11448 (histone demethylase JMJD3 [EC:1.14.11.-]) KDM6B Kdm6b
ko:K11447 (histone demethylase [EC:1.14.11.-]) KDM6A
UTY
Kdm6a
Uty
gi:17567315
gi:17550694
tag-279
utx-1
Utx
ko:K06709 (jumonji domain-containing protein 2 [EC:1.14.11.-]) KDM4B
KDM4C
KDM4D
KDM4A
Kdm4b
Kdm4a
Kdm4d
Kdm4c
jmjd-2 Kdm4B
ko:K11449 (jumonji domain-containing protein 1 [EC:1.14.11.-]) JMJD1C
KDM3B
KDM3A
Kdm3a
Jmjd1c
Kdm3b
gi:28571604 gi:186478394
ko:K11445 (JmjC domain-containing histone demethylation protein 1D/E/F) JHDM1D Jhdm1d
ko:K10276 (F-box and leucine-rich repeat protein 10/11 [EC:1.14.11.27]) KDM2A
KDM2B
Kdm2a
Kdm2b
gi:32565554 gi:281361422 JHD1 epe1
ko:K11439 (protein arginine N-methyltransferase 8 [EC:2.1.1.-]) PRMT8 Prmt8
ko:K11438 (protein arginine N-methyltransferase 7 [EC:2.1.1.-]) PRMT7 Prmt7 gi:17509621 Art7 PRMT7
ko:K11437 (protein arginine N-methyltransferase 6 [EC:2.1.1.-]) PRMT6 Prmt6 PRMT6
ko:K02516 (protein arginine N-methyltransferase 5 [EC:2.1.1.125]) PRMT5 Prmt5 prmt-5 csul HSL7 skb1 SKB1
ko:K05931 (histone-arginine methyltransferase CARM1 [EC:2.1.1.125]) CARM1 Carm1 Art4 PRMT4B
PRMT4A
ko:K11436 (protein arginine N-methyltransferase 3 [EC:2.1.1.-]) PRMT3 Prmt3 Art3 rmt3 PRMT3
ko:K11435 (protein arginine N-methyltransferase 2 [EC:2.1.1.-]) PRMT2 Prmt2
ko:K11434 (protein arginine N-methyltransferase 1 [EC:2.1.1.-]) PRMT1 Prmt1 gi:17566490 Art1 HMT1 rmt1 PRMT11
PRMT1A
ko:K11429 (histone-lysine N-methyltransferase SUV420H [EC:2.1.1.43]) SUV420H1
SUV420H2
Suv420h2
Suv420h1
set-4 Suv4-20 set9
ko:K11419 (histone-lysine N-methyltransferase SUV39H [EC:2.1.1.43]) SUV39H1
SUV39H2
Suv39h1
Suv39h2
Su(var)3-9 clr4
ko:K11426 (SET and MYND domain-containing protein) SMYD1
SMYD2
SMYD3
Smyd1
Smyd2
Smyd3
set-14
set-30
set-18
Bzd set6 SDG37
ko:K11433 (histone-lysine N-methyltransferase SETMAR [EC:2.1.1.43]) SETMAR Setmar set-23 gi:161078181
ko:K11421 (histone-lysine N-methyltransferase SETDB [EC:2.1.1.43]) SETDB1
SETDB2
Setdb2
Setdb1
met-2 egg
ko:K11428 (histone-lysine N-methyltransferase SETD8 [EC:2.1.1.43]) SETD8 Setd8 set-1 pr-set7
ko:K11431 (histone-lysine N-methyltransferase SETD7 [EC:2.1.1.43]) SETD7 Setd7
ko:K11423 (histone-lysine N-methyltransferase SETD2 [EC:2.1.1.43]) SETD2 Setd2 Set2 SET2 set2
ko:K11422 (histone-lysine N-methyltransferase SETD1 [EC:2.1.1.43]) SETD1B
SETD1A
Setd1b
Setd1a
set-2 gi:62862148 SET1 set1
ko:K11432 (PR domain zinc finger protein 2) PRDM2 Prdm2
ko:K11425 (histone-lysine N-methyltransferase NSD3 [EC:2.1.1.43]) WHSC1L1 Whsc1l1
ko:K11424 (histone-lysine N-methyltransferase NSD1/2 [EC:2.1.1.43]) NSD1
WHSC1
Whsc1
Nsd1
Mes-4
ko:K09189 (histone-lysine N-methyltransferase MLL5 [EC:2.1.1.43]) MLL5 Mll5
ko:K14959 (histone-lysine N-methyltransferase MLL4 [EC:2.1.1.43]) MLL4 Wbp7
ko:K09188 (histone-lysine N-methyltransferase MLL3 [EC:2.1.1.43]) MLL3 Mll3 set-16 trr
ko:K09187 (histone-lysine N-methyltransferase MLL2 [EC:2.1.1.43]) MLL2 Mll2
ko:K09186 (histone-lysine N-methyltransferase MLL1 [EC:2.1.1.43]) MLL Mll1 trx
ko:K11430 (enhancer of zeste [EC:2.1.1.43]) EZH1
EZH2
Ezh1
Ezh2
E(z) SWN
CLF
MEA
ko:K11420 (euchromatic histone-lysine N-methyltransferase [EC:2.1.1.43]) EHMT2
EHMT1
Ehmt2
Ehmt1
G9a
ko:K11427 (histone-lysine N-methyltransferase, H3 lysine-79 specific [EC:2.1.1.43]) DOT1L Dot1l gi:71994293
gi:71991708
gi:17568207
gi:17570285
gpp DOT1
ko:K06101 (histone-lysine N-methyltransferase ASH1L [EC:2.1.1.43]) ASH1L Ash1l lin-59 ash1
ko:K11418 (histone deacetylase 11 [EC:3.5.1.98]) HDAC11 Hdac11 gi:193207430 HdacX HDA2
ko:K11417 (NAD-dependent deacetylase sirtuin 7 [EC:3.5.1.-]) SIRT7 Sirt7 Sirt7
ko:K11416 (mono-ADP-ribosyltransferase sirtuin 6 [EC:2.4.2.31]) SIRT6 Sirt6 Sir-2.4 Sirt6 SRT1
ko:K11415 (NAD-dependent deacetylase sirtuin 5 [EC:3.5.1.-]) SIRT5 Sirt5
ko:K11414 (NAD-dependent deacetylase sirtuin 4 [EC:3.5.1.-]) SIRT4 Sirt4 sir-2.3
sir-2.2
Sirt4
ko:K11413 (NAD-dependent deacetylase sirtuin 3 [EC:3.5.1.-]) SIRT3 Sirt3
ko:K11412 (NAD-dependent deacetylase sirtuin 2 [EC:3.5.1.-]) SIRT2 Sirt2 Sirt2
ko:K11411 (NAD-dependent deacetylase sirtuin 1 [EC:3.5.1.-]) SIRT1 Sirt1 sir-2.1 Sir2
ko:K11409 (histone deacetylase 9 [EC:3.5.1.98]) HDAC9 Hdac9
ko:K11408 (histone deacetylase 7 [EC:3.5.1.98]) HDAC7 Hdac7
ko:K11407 (histone deacetylase 6/10 [EC:3.5.1.98]) HDAC6
HDAC10
Hdac6
Hdac10
gi:17540332 HDAC6 HDA1 clr3 HDA05
HDA18
ko:K11406 (histone deacetylase 4/5 [EC:3.5.1.98]) HDAC5
HDAC4
Hdac5
Hdac4
Hda-4 HDAC4
ko:K11484 (histone deacetylase HOS3 [EC:3.5.1.98]) HOS3
ko:K11483 (histone deacetylase HOS2 [EC:3.5.1.98]) HOS2 hos2
ko:K11482 (histone deacetylase HOS1 [EC:3.5.1.98]) HOS1
ko:K11405 (histone deacetylase 8 [EC:3.5.1.98]) HDAC8 Hdac8
ko:K11404 (histone deacetylase 3 [EC:3.5.1.98]) HDAC3 Hdac3 Hdac3
ko:K06067 (histone deacetylase 1/2 [EC:3.5.1.98]) HDAC1
HDAC2
Hdac1
Hdac2
hda-2
hda-1
hda-3
Rpd3 RPD3 clr6 hda17
HDA9
HD1
HDA7
HDA6
ko:K02223 (circadian locomoter output cycles kaput protein [EC:2.3.1.48]) CLOCK Clock Clk
ko:K11256 (nuclear receptor coactivator 3 [EC:2.3.1.48]) NCOA3 Ncoa3
ko:K11255 (nuclear receptor coactivator 2) NCOA2 Ncoa2
ko:K09101 (nuclear receptor coactivator 1 [EC:2.3.1.48]) NCOA1 Ncoa1
ko:K11310 (general transcription factor 3C polypeptide 4 [EC:2.3.1.48]) GTF3C4 Gtf3c4 gi:24656139 sfc9
ko:K11309 (regulator of Ty1 transposition protein 109) RTT109 rtt109
ko:K07739 (elongator complex protein 3 [EC:2.3.1.48]) ELP3 Elp3 elpc-3 Elp3 ELP3 elp3 ELO3
ko:K11306 (histone acetyltransferase MYST4 [EC:2.3.1.48]) MYST4 Myst4 enok
ko:K11305 (histone acetyltransferase MYST3 [EC:2.3.1.48]) MYST3 Myst3
ko:K11307 (histone acetyltransferase MYST2 [EC:2.3.1.48]) MYST2 Myst2 chm
ko:K11308 (histone acetyltransferase MYST1 [EC:2.3.1.48]) MYST1 Myst1 mys-2 mof
gi:24650814
HAM1
HAM2
ko:K11304 (histone acetyltransferase HTATIP [EC:2.3.1.48]) KAT5 Kat5 mys-1 Tip60 ESA1 mst1
ko:K03125 (transcription initiation factor TFIID subunit 1) TAF1L
TAF1
Taf1
Taf1
taf-1
taf-1
Taf1
Taf1
TAF1
TAF1
taf111
taf111
HAF2
HAF2
HAF01
HAF01
ko:K04498 (E1A/CREB-binding protein [EC:2.3.1.48]) CREBBP
EP300
Crebbp
Ep300
cbp-1 nej HAC12
HAC4
HAC2
HAC1
HAC5
ko:K06062 (histone acetyltransferase [EC:2.3.1.48]) KAT2A
KAT2B
Kat2a
Kat2b
pcaf-1 Pcaf GCN5 gcn5 HAG1
ko:K11303 (histone acetyltransferase 1 [EC:2.3.1.48]) HAT1 Hat1 tag-235 gi:24644413 HAT1 hat1 HAG2

References:

  • Histone modifications in response to DNA damage.

    , , : [PUBMED]
  • More than just a focus: The chromatin response to DNA damage and its role in genome integrity maintenance.

    , , : [PUBMED]
  • The histone code at DNA breaks: a guide to repair?

    , , : [PUBMED]
  • Histone demethylation by a family of JmjC domain-containing proteins.
    Tsukada Y., Fang J., Erdjument-Bromage H., Warren ME., Borchers CH., Tempst P., Zhang Y.
    Nature, 2006 Feb, 439:811-6 [PUBMED]
  • Histone methyltransferase Suv39h1 represses MyoD-stimulated myogenic differentiation.
    Mal AK.
    EMBO J., 2006 Jul, 25:3323-34 [PUBMED]
  • Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1.
    Kalakonda N., Fischle W., Boccuni P., Gurvich N., Hoya-Arias R., Zhao X., Miyata Y., Macgrogan D., Zhang J., Sims JK., Rice JC., Nimer SD.
    Oncogene, 2008 Jul, 27:4293-304 [PUBMED]
  • Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein.
    Kuzmichev A., Nishioka K., Erdjument-Bromage H., Tempst P., Reinberg D.
    Genes Dev., 2002 Nov, 16:2893-905 [PUBMED]
  • Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ domain) and copurifies with deubiquitinating enzymes.
    Hook SS., Orian A., Cowley SM., Eisenman RN.
    Proc. Natl. Acad. Sci. U.S.A., 2002 Oct, 99:13425-30 [PUBMED]
  • Histone deacetylase 1 phosphorylation promotes enzymatic activity and complex formation.
    Pflum MK., Tong JK., Lane WS., Schreiber SL.
    J. Biol. Chem., 2001 Dec, 276:47733-41 [PUBMED]
  • Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress.
    Ward IM., Chen J.
    J. Biol. Chem., 2001 Dec, 276:47759-62 [PUBMED]
  • Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage.
    Wang H., Zhai L., Xu J., Joo HY., Jackson S., Erdjument-Bromage H., Tempst P., Xiong Y., Zhang Y.
    Mol. Cell, 2006 May, 22:383-94 [PUBMED]
  • Histone fold protein Dls1p is required for Isw2-dependent chromatin remodeling in vivo.
    McConnell AD., Gelbart ME., Tsukiyama T.
    Mol. Cell. Biol., 2004 Apr, 24:2605-13 [PUBMED]

Last modification date: Oct. 11, 2011