Histone Methylation (히스톤 메틸화) is a process by which methyl groups are transferred to amino acids of histone proteins that make up nucleosomes, which the DNA double helix wraps around to form chromosomes. (http://en.wikipedia.org/wiki/Histone_methylation)

Histone에 메틸기를 붙히거나 떼어냄으로써 인근 유전자의 발현을 끄거나 켜는 조절 기능. Histone modification의 한가지.

Histone methyltransferase (HMTs) #

Protein methyltransferases(PMT)는 다음과 같은 것들이 있음 (보통 SET(Suppressor of variegation, Enhancer of zeste, Trithorax)-domain을 가짐)

• Protein lysine methyltransferases (PKMT)

  • EHMT family
    • EHMT1 (KMT1D (GLP) - H3K9, H3K27 (repressor)
    • EHMT2 (KMT1C, G9a, G9A) - H3K9, H3K27, H3K56 (repressor)
  • KMT2 family
    • MLL (KMT2A, MLL1) - H3K4, H4K16ac (activator)
    • MLL2 (KMT2D) - H3K4 (activator)
    • MLL3 (KMT2C) - H3K4 (activator)
    • MLL4 (KMT2B) - H3K4 (activator)
    • MLL5 (KMT2E) - H3K4 (activator)
    • SETD1A (KMT2F) - H3K4 (activator)
    • SETD1B (KMT2G) - H3K4 (activator)
    • SETDB1 (KMT1E)
    • SETDB2 (KMT1F)
    • SETD3
    • SETD4
    • SETD5
    • SETD6
    • SETMAR
  • SMYD family
    • SMYD1 (KMT3D) - H3K4 (activator)
    • SMYD2 (KMT3C) - H3K4, H3K36 (activator)
    • SMYD3 (KMT3E) - H3K4, H3K5 (activator)
    • SMYD4 (repressor)
    • SMYD5 - H4K20 (repressor)
  • NSD family
    • NSD1 (KMT3B) - H3K36, H4K20 (activator)
    • NSD2 (KMT3G, WHSC1) - H3K36, H4K20, H4K44 (repressor)
    • NSD3 (KMT3F, WHSC1L1) - H3K36, H3K4, H3K27 (both)
  • SET7 & SET8
    • SETD7 (KMT7, SET7, SET9) - H3K4 (activator)
    • SETD8 (KMT5A, SET8, PR-SET7) - H4K20 (repressor)
  • SUV family
    • SUV39H1 (KMT1A)
    • SUV39H2 (KMT1B)
    • SUV420H1 (KMT5B) - H4K20
    • SUV420H2 (KMT5C) - H4K20
  • PRDM family
    • PRDM1
    • PRDM2
    • PRDM3 (MECOM)
    • PRDM4
    • PRDM5
    • PRDM6
    • PRDM7
    • PRDM8
    • PRDM9
    • PRDM10
    • PRDM11
    • PRDM12
    • PRDM13
    • PRDM14
    • PRDM15
    • PRDM16
  • Etc
    • EZH1 (KMT6B) - H3K27
    • EZH2 (KMT6A) - H3K9, H3K27
    • ASH1L (KMT2H)
    • WHSC1
    • WHSC1L1

• Protein arginine methylatransferase (PRMT)

  • PRMT1
  • PRMT2
  • PRMT3
  • PRMT4
  • PRMT5
  • PRMT6
  • PRMT7 ~ 9
• DOT1L (SET domain 없음)

cBioPortal 쿼리용

EHMT1 EHMT2 KMT2A KMT2D KMT2C KMT2B KMT2E SETD1A SETD1B SETDB1 SETDB2 SETD3 SETD4 SETD5 SETD6 SETMAR SMYD1 SMYD2 SMYD3 SMYD4 SMYD5 NSD1 WHSC1 WHSC1L1 SETD7 KMT5A SUV39H1 SUV39H2 KMT5B KMT5C PRDM1 PRDM2 MECOM PRDM4 PRDM5 PRDM6 PRDM7 PRDM8 PRDM9 PRDM10 PRDM11 PRDM12 PRDM13 PRDM14 PRDM15 PRDM16 EZH1 EZH2 ASH1L WHSC1 WHSC1L1

Lysine methylation is associated to

• Gene silencing: H3K9, H3K27, H4K20
• Gene activating: H3K4, H3K36, H2K79

MLL 유전자의 SET domain이 소실되면서 Leukemia 발병. 보통 DOT1L과 fusion을 이루면서 기능을 상실함

관련 유전자들: DOT1L, Menin, ASH2L, SMYD3, EZH2, Suv39h1, G9a

Histone demethylase #

다음과 같은 Demethylase들이 잘 알려져 있다.

1. KDM(LSD) family (amine oxidation process)
   • LSD1 (KDM1A) - H3K4, H3K9 (both)
   • LSD2 (KDM1B) - H3K4 (repressor)
2. FBX
   • FBXL10 (KDM2B) - H3K36, H3K4 (repressor)
   • FBXL11 (KDM2A) - H3K36 (repressor)
3. hydroxylation of methyl group
   1. Jumanji (JmjC) domain
      • JMJD1A (KDM3A) - H3K9 (activator)
      • JMJD1C (KDM3C) - H3K9 (activator)
      • JMJD2A (KDM4A) - H3K9, H3K36, H1.4K26 (repressor)
      • JMJD2B (KDM4B) - H3K9, H3K36, H1.4K26 (repressor)
      • JMJD2C (KDM4C) - H3K9, H3K36, H1.4K26 (repressor)
      • JMJD2D (KDM4D) - H3K9, H3K36, H1.4K26 (repressor)
      • JMJD3 (KDM6B) - H3K27 (repressor)
      • JMJD5 (KDM8) - H3K4, H3K36 (repressor)
   2. JARID
      • JARID1A (KDM5A, RBP2) - H3K4 (repressor)
      • JARID1B (KDM5B, (PLU-1) - H3K4 (repressor)
      • JARID1C (KDM5C) - H3K4 (repressor)
      • JARID1D (KDM5D) - H3K4 (repressor)
4. SWIRM domain
5. Etc
   • JHDM1D (KDM7A) - H3K9 (activator)
   • JHDM2B (KDM3B) - H3K9 (activator)
   • UTX (KDM6A) - H3K27 (repressor)
   • UTY (KDM6C) - H3K36 (repressor)
   • PHF2 (KDM7C) - H3K9, H3K4 (both)
   • PHF8 (KDM7B) - H3K9, H3K27 (both)
   • MINA - H3K9 (activator)
   • NO66 (C14orf169) - H3K4, H3K36 (repressor)

cBioPortal 쿼리용

KDM1A KDM1B KDM2B KDM2A KDM3A KDM4A KDM4B KDM4C KDM4D KDM6B JMJD1C KDM8 KDM5A KDM5B KDM5C KDM5D KDM7A KDM3B KDM6A UTY PHF2 PHF8 MINA C14ORF169

인지하는 도메인 #

1. PHD (plant homeodomain)
2. Chromodomain
3. PcG

관련 논문 #

• Dysregulation of histone methyltransferases in breast cancer – Opportunities for new targeted therapies? Molecular Oncology 2016-09-23

Incoming Links #

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• Covalent modifications of histones during development and disease pathogenesis
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• Cancer epigenetics
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• LSD1
• MLL2
• SMYD3
• WHSC1L1

[Medical Scholarly Articles] About (MedicalScholarlyArticle 2) #

• Genetic alterations of histone lysine methyltransferases and their signi cance in breast cancer

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