Table 1 The main regulatory mechanisms of transcription factor lysine methylation

From: Lysine methylation of transcription factors in cancer

Mechanism

Substratea

Enzymeb

Tumor type

Transcription activity

References

Protein stability

RORαK38me1

EZH2

Breast cancer

Inhibition

60

 

RelAK314me1

K315me1

SET7

MEFs (mouse cardio myocytes),

U2OS(osteosarcoma cell), A549(NSCLC cell)

Inhibition

62

Nuclear localization

P53K372me1

SET7

293F, U2OS(osteosarcoma cell), H1299(NSCLC cell)

Activation

64

 

ERαK302me1

SET7

Breast cancer

Activation

65

DNA-binding affinity

P53K370me1

SMYD2

H1299(NSCLC cell), U2OS(osteosarcoma cell),

BJ-DNp53(fibroblast cell)

Inhibition

66

 

HIF1αK32me1

SET7

RCC4(renal carcinoma cell)

Inhibition

70

 

HIF2αK29me1

SET7

RCC4(renal carcinoma cell)

Inhibition

70

 

P53K382me1

SET8

U2OS(osteosarcoma cell), H1299(NSCLC cell)

Inhibition

67

 

STAT3

K140me2

SET7

DLD1(colon cancer cell)

Inhibition

57

 

RelAK37me1

SET7

293T

Activation

73

 

RelAK218me1,

K221me2

NSD1

293C6, HT29(colon cancer cell)

Activation

74

 

ARK632me*

SET7

Prostate cancer cell

Activation

72

 

YY1K173me1,

K411me1

SET7

HeLa(cervical carcinoma)

Activation

95

 

YY2 K247me1

SET7

HeLa(cervical carcinoma)

Activation

96

Protein–protein binding

RelAK310me1

SETD6

293T, U2OS(osteosarcoma cell),

THP1(mononuclear macrophage)

Inhibition

82

 

RBK860me1

SMYD2

293T, U2OS(osteosarcoma cell),

NIH3T3(mouse embryonal fibroblast cell)

Activation

76

 

RBK873me1

SET7

U2OS(osteosarcoma cell), SAOS2(osteosarcoma cell),

C2C12(myoblast), CC42 (fibroblast cell)

Activation

77

 

P53K382me2

Unknown

U2OS(osteosarcoma cell)

Activation

75

Crosstalk with other PTMs

GATA4

K299me1

EZH2

HL1(mouse cardio myocytes)

Inhibition

97

 

RBK810me1

SET7

U2OS(Osteosarcoma cell)

Inhibition

81

 

ERαK266me1

SMYD2

Breast cancer

Inhibition

79

 

STAT3K180me*

EZH2

Glioblastoma

Activation

80

  1. Asterisks indicate that the methylation status is unknown
  2. aMethylation substrate, lysine site, and methylation degree
  3. bLysine methyl transferases and synonyms: SET7 (KMT7, SET7/9, SET9, SETD7); EZH2 (KMT6A/KMT6); SET8 (PR-Set7, KMT5A, SETD8); NSD1 (KMT3B); SMYD2 (KMT3C)