Histone Demethylases

Histone demethylases (KDMs) are a family of enzymes that catalyze the removal of methyl groups from lysine and arginine residues on histone tails. They reverse the methylation of lysine and arginine residues that is catalyzed by histone methyltransferases.

Products
Background
Literature
Gene Data

Inhibitors

Cat No Product Name / Activity
4684 Daminozide
Selective KDM2/7 inhibitor
4593 GSK J1
Potent JMJD3/UTX inhibitor
4688 GSK J2
Inactive isomer of GSK J1 (Cat. No. 4593)
4594 GSK J4
Histone KDM inhibitor; cell permeable
4689 GSK J5
Inactive isomer of GSK J4 (Cat. No. 4594); cell permeable
5361 GSK LSD 1 dihydrochloride
Potent and selective LSD1 inhibitor
6124 (R)-2-Hydroxyglutaric acid disodium salt
KDM4A inhibitor; also NF-κB activator
4464 IOX 1
Histone demethylase inhibitor; cell permeable
4972 JIB 04
Pan Jumonji inhibitor; active in vivo
5287 NSC 636819
KDM4A/KDM4B inhibitor
5930 PBIT
JARID1 (Jumonji AT-Rich Interactive Domain 1) inhibitor
4977 RN 1 dihydrochloride
LSD1 inhibitor
5714 S 2101
LSD1 inhibitor
5089 TC-E 5002
Selective KDM2/7 inhibitor
3852 Tranylcypromine hydrochloride
Irreversible inhibitor of LSD1; also inhibits MAO

Histone demethylases (KDMs) are a family of enzymes that catalyze the removal of methyl groups from lysine and arginine residues on histone tails. They reverse the methylation of lysine and arginine residues that is catalyzed by histone methyltransferases.

The first histone demethylase to be discovered was lysine-specific demethylase 1 (LSD1), but further research identified an additional family of histone demethylases; the Jumonji C domain-containing demethylases (JMJD). JMJDs require both Fe2+ and 2-oxoglutarate as co-factors for histone demethylation, whilst the catalysis carried out by LSD1 is dependent on the presence of a protonated nitrogen atom. The JMJD family of demethylases remove methyl groups from tri-methylated histone arginine and lysine residues whereas LSD1 demethylates mono- and di-methylated lysine residues on histone H3 (H3K4 and H3K9), but cannot demethylate tri-methylated residues. To date, only one member of the JMJD family - JMJD6 - has been shown to specifically demethylate arginine residues.

The removal of methyl groups from histone lysine and arginine residues is typically associated with transcriptional repression, but this is not true in all cases; the histone demethylase JMJD2A has recently been shown to function as a transcriptional co-activator of androgen receptor responsive genes.

In addition to co-activation of androgen receptor responsive genes, the biological functions of JMJDs include stem cell self-renewal, the inflammatory response and cell differentiation. JMJD1A has also been shown to be essential during spermatogenesis. LSD1 is also involved in a wide array of biological processes including cell proliferation, chromosome segregation and embryonic development, but more recently has been identified as a potential target for cancer therapeutics.

Literature for Histone Demethylases

Cancer

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

  • Cancer Metabolism
  • Epigenetics in Cancer
  • Receptor Signaling
  • Cell Cycle and DNA Damage Repair
  • Angiogenesis
  • Invasion and Metastasis
Epigenetics

Epigenetics Scientific Review

Written by Susanne Müller-Knapp and Peter J. Brown, this review gives an overview of the development of chemical probes for epigenetic targets, as well as the impact of these tool compounds being made available to the scientific community. In addition, their biological effects are also discussed. Epigenetic compounds available from Tocris are listed.

Epigenetics

Epigenetics Research Bulletin

Produced by Tocris and updated in 2014, the epigenetics research bulletin gives an introduction into mechanisms of epigenetic regulation, and highlights key Tocris products for epigenetics targets including:

  • Bromodomains
  • DNA Methyltransferases
  • Histone Deacetylases
  • Histone Demethylases
  • Histone Methyltransferases

Histone Demethylase Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
KDM1A Human KDM1A NM_015013 O60341
Mouse Kdm1a NM_133872 Q6ZQ88
Rat Kdm1a NM_001130098 NP_001123570
KDM1B Human KDM1B NM_153042 Q8NB78
Mouse Kdm1b NM_172262 Q8CIG3
Rat Kdm1b NM_001107343 NP_001100813
KDM2A Human KDM2A NM_012308 Q9Y2K7
Mouse Kdm2a NM_001001984 P59997
Rat Kdm2a NM_001108515 NP_001101985
KDM2B Human KDM2B NM_032590 Q8NHM5
Mouse Kdm2b NM_001003953 Q6P1G2
Rat Kdm2b NM_001100679 NP_001094149
KDM3A Human KDM3A NM_018433 Q9Y4C1
Mouse Kdm3a NM_173001 Q6PCM1
Rat Kdm3a NM_175764 NP_786940
KDM3B Human KDM3B NM_016604 Q7LBC6
Mouse Kdm3b NM_001081256 Q6ZPY7
Rat - - -
KDM4A Human KDM4A NM_014663 O75164
Mouse Kdm4a NM_001161823 Q8BW72
Rat Kdm4a NM_001107966 NP_001101436
KDM4B Human KDM4B XM_290852 O94953
Mouse Kdm4b NM_172132 Q91VY5
Rat LOC301128 NM_001044236 NP_001037701
KDM4C Human KDM4C NM_015061 Q9H3R0
Mouse Kdm4c NM_144787 Q8VCD7
Rat Kdm4c NM_001106663 NP_001100133
KDM4D Human KDM4D NM_018039 Q6B0I6
Mouse Kdm4d NM_173433 Q3U2K5
Rat Kdm4d NM_001079712 NP_001073180
KDM4E Human KDM4E NM_001161630 B2RXH2
Mouse - - -
Rat - - -
KDM5A Human KDM5A NM_005056 P29375
Mouse Kdm5a NM_145997 Q3UXZ9
Rat Kdm5a XM_002726483 XP_002726529
KDM5B Human KDM5B NM_006618 Q9UGL1
Mouse Kdm5b NM_152895 Q80Y84
Rat Kdm5b NM_001107177 NP_001100647
KDM5C Human KDM5C NM_004187 P41229
Mouse Kdm4c NM_013668 P41230
Rat - - -
KDM5D Human KDM5D NM_004653 Q9BY66
Mouse Kdm5d NM_011419 Q62240
Rat - - -
KDM6A Human KDM6A NM_021140 O15550
Mouse Kdm6a NM_009483 O70546
Rat Kdm6a XM_002727525 XP_002727571
KDM6B Human KDM6B XM_043272 O15054
Mouse Kdm6b NM_001017426 Q5NCY0
Rat Kdm6b NM_001108829 NP_001102299
KDM8 Human KDM8 NM_024773 Q8N371
Mouse Jmjd5 NM_029842 Q9CXT6
Rat Kdm8 NM_001037196 Q497B8
FBXL19 Human FBXL19 NM_019085 Q6PCT2
Mouse Fbxl19 NM_172748 Q6PB97
Rat - - -
PHF2 Human PHF2 NM_005392 O75151
Mouse Phf2 NM_011078 Q9WTU0
Rat Phf2 NM_001107342 NP_001100812
PHF8 Human PHF8 NM_015107 Q9UPP1
Mouse Phf8 NM_001113354 NP_001106825
Rat RGD1561065 NM_001108253 NP_001101723