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Table 3 Epigenetic mechanisms of histone modifications in organ fibrosis

From: Epigenetics as a versatile regulator of fibrosis

Histone modification

Function

Molecule

Target genes

Transcriptional regulation

Effect on fibrosis

Organ

Refs.

Acetylation

Acetylase

P300

CCL2

Activation

Pro

Lung

[53]

NOX4

Activation

Pro

Lung

[54]

Reader

BRD4

SNAI1, ZEB1, TWIST1

Activation

Pro

Lung

[57]

NOX4

Activation

Pro

Lung

[54]

SERTAD4

Activation

Pro

Heart

[59]

NPPA, NPPB, CTGF

Activation

Pro

Heart

[58]

Deacetylation

Deacetylase (Class I HDACs)

HDAC1, HDAC2, HDAC3

COX-2

Repression

Pro

Lung

[78]

HDAC1

COL1A1

Repression

Anti

Skin

[80]

HDAC1

MAP2K3

Repression

Anti

Heart

[83]

HDAC3

WIF-1

Repression

Pro

Skin

[81]

HDAC8

PPARγ

Repression

Pro

Lung

[82]

Deacetylase (Class II HDACs)

HDAC4, HDAC5, HDAC7

Thy-1

Repression

Pro

Lung

[84]

HDAC4

SIRT1

Repression

Pro

Liver

[91]

HDAC4

MMP9

Repression

Pro

Liver

[88]

HDAC7

HGF

Repression

Pro

Liver

[89]

HDAC7

PGC1α

Repression

Pro

Lung

[85]

Deacetylase (Class III HDACs)

SIRT1

MMP9

Repression

Anti

Lung

[95]

SIRT3

FOS

Repression

Anti

Heart

[93]

SIRT6

IGR signaling related genes

Repression

Anti

Heart

[94]

Methylation

Methylase (H3K27)

EZH2

Smad7, PTEN

Repression

Pro

Kidney

[101]

EZH2

CTGF, CCL2

Repression

Anti

Kidney

[105]

EZH2

Dkk1

Repression

Pro

Liver

[102]

EZH2

PPARγ

Repression

Pro

Liver

[103]

/

FRA2

Repression

Anti

Skin

[104]

Methylase (H3K9)

G9a

PGC1α

Repression

Pro

Lung

[112]

G9a

IP-10

Repression

Pro

Lung

[79]

/

Fas

Repression

Pro

Lung

[87]

G9a

E-cadherin

Repression

Pro

Lung

[116]

G9a

Klotho

Repression

Pro

Kidney

[114]

Methylase (H3K27 & H3K9)

EZH2, G9a

CXCL10, COX-2

Repression

Pro

Lung

[109]

Methylase (H3K4)

COMPASS

COL1A1, COL1A2, α-SMA

Activation

Pro

Liver

[127]

COMPASS

COL1A1, COL1A2

Activation

Pro

Kidney

[126]

SET7/9

TGF-β1

Activation

Pro

Liver

[128]

SET7/9

COL1A1, CTGF, PAI-1

Activation

Pro

Kidney

[129]

ASH1

COL1A1, COL1A2, α-SMA, TIMP1, TGF-β1

Activation

Pro

Kidney

[130]

Demethylase (H3K27)

JMJD3(KDM6B)

CTGF, CCL2

Activation

Pro

Kidney

[105]

JMJD3(KDM6B)

FRA2

Activation

Pro

Skin

[107]

JMJD3(KDM6B)

XIAP, survivin

Activation

Anti

Lung

[106]

Demethylase (H3K9)

JMJD1A(KDM3A)

YAP1, TGF-β2

Activation

Pro

Kidney

[118]

JMJD1A(KDM3A)

CTGF

Activation

Pro

Kidney

[119]

JMJD1A(KDM3A)

TIMP1

Activation

Pro

Heart

[120]

JMJD1A(KDM3A)

PPARγ

Activation

Anti

Liver

[122]

KDM4A/B/C

miR-29

Activation

Anti

Liver

[123]

KDM4D

TLR4

Activation

Pro

Liver

[121]