Unveiling the Role of Histone Methyltransferases in Psoriasis Pathogenesis: Insights from Transcriptomic Analysis
Abstract
1. Introduction
2. Results
2.1. SET Domain-Containing Histone Lysine Methyltransferases with Altered Expression in Psoriasis
2.2. Histone Lysine Methyltransferase Complex Members Affected by Altered Expression in Psoriasis
2.3. Alterations in the Expression of Seven-β-Strand Lysine Methyltransferases in Psoriasis
2.4. Modifications in the Expression of Seven-β-Strand Arginine Methyltransferases in Psoriasis
2.5. Diversity of Methyltransferase Transcript Variants and Encoded Isoforms in Psoriasis
3. Discussion
3.1. Histone Methyltransferase-Related Alterations in Psoriasis
3.1.1. SET Domain Methyltransferases
EZ Subfamily of Methyltransferases
SET1 Subfamily of Methyltransferases
SET2 Subfamily of Methyltransferases
SMYD Subfamily of Methyltransferases
SUV39 Subfamily of Methyltransferases
SUV4-20 Subfamily Methyltransferases
PRDM Subfamily of Methyltransferases
Other SET Domain-Containing Histone Lysine Methyltransferases: SETD7 and SETD8
3.1.2. Seven-β-Strand (7BS) Methyltransferases
4. Materials and Methods
4.1. Guidelines for Establishing a Combined Psoriasis Transcriptome Sequencing Dataset Based on Literature Sources
4.2. Processing and Differential Expression Analysis of RNA Sequencing Data
4.3. Screening for Histone Methylation-Related DETs in Psoriasis
4.4. Analysis of Protein Isoforms Derived from Differentially Expressed Transcripts
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
7BS | seven-β-strand |
AEBP2 | AE (Adipocyte Enhancer)-Binding Protein 2 |
ANTKMT | Adenine Nucleotide Translocase Lysine Methyltransferase |
ASH1L | ASH1 Like Histone Lysine Methyltransferase |
ASH2L | ASH2 Like Histone Lysine Methyltransferase Complex Subunit |
ATPSCKMT | ATP Synthase C Subunit Lysine N-Methyltransferase |
CAMKMT | Calmodulin-Lysine N-Methyltransferase |
CD4+ T cells | Cluster of Differentiation 4 Positive T cells |
CD8+ T cells | Cluster of Differentiation 8 Positive T cells |
CDK2 | Cyclin Dependent Kinase 2 |
CDKN1A | Cyclin Dependent Kinase Inhibitor 1A |
CSKMT | Citrate Synthase Lysine Methyltransferase |
COMPASS | Complex Proteins Associated with SET1 |
c-MYC | MYC Proto-Oncogene, BHLH transcription Factor |
CXCL10 | C-X-C Motif Chemokine Ligand 10 |
CXXC1 | CXXC Finger Protein 1 |
DET | Differentially Expressed Transcript |
DNA | Deoxyribonucleic acid |
DOT1L | DOT1 Like Histone Lysine Methyltransferase |
DPY30 | Dpy-30 Histone Methyltransferase Complex Regulatory Subunit |
E2F | E2F Transcription Factor |
EED | Embryonic Ectoderm Development |
EEF1AKMT1 | EEF1A Lysine Methyltransferase 1 |
EEF1AKMT2 | EEF1A Lysine Methyltransferase 2 |
EEF1AKMT3 | EEF1A Lysine Methyltransferase 3 |
EEF1AKMT4 | EEF1A Lysine Methyltransferase 4 |
EEF2KMT | Eukaryotic Elongation Factor 2 Lysine Methyltransferase |
EHMT1 | Euchromatic Histone Lysine Methyltransferase 1 |
EHMT2 | Euchromatic Histone Lysine Methyltransferase 2 |
EPOP | Elongin BC And Polycomb Repressive Complex 2 Associated Protein |
ETFBKMT | Electron Transfer Flavoprotein Beta Subunit Kinase Methyltransferase |
EZH1 | Enhancer of Zeste 1 Polycomb Repressive Complex 2 Subunit |
EZH2 | Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit |
GATA3 | GATA Binding Protein 3 |
GO | Gene Ontology |
H2AR11me2 | Histone 2A Arginine 11 Dimethylation |
H2AR29me2 | Histone 2A Arginine 29 Dimethylation |
H2AR3me1 | Histone 2A Arginine 3 Monomethylation |
H2AR3me2 | Histone 2A Arginine 3 Dimethylation |
H2ARme1/2 | Histone 2A Arginine Monomethylation/Dimethylation |
H2AZ | Histone variantH2A.Z |
H2AZK7 | Histone variantH2A.Z Lysine 7 Methylation |
H2B | Histone 2B |
H2BR29me1 | Histone 2B Arginine 29 Monomethylation |
H2BR31me1 | Histone 2B Arginine 31 Monomethylation |
H2BR33me1 | Histone 2B Arginine 33 Monomethylation |
H3 | Histone 3 |
H3K18me1 | Histone 3 Lysine 18 Monomethylation |
H3K27 | Histone 3 Lysine 27 |
H3K27me1/2/3 | Histone 3 Lysine 27 Mono-/Di-/Trimethylation |
H3K27me3 | Histone 3 Lysine 27 Trimethylation |
H3K36 | Histone 3 Lysine 36 |
H3K36me1/2 | Histone 3 Lysine 36 Mono-/Dimethylation |
H3K36me2 | Histone 3 Lysine 36 Dimethylation |
H3K36me3 | Histone 3 Lysine 36 Trimethylation |
H3K4 | Histone 3 Lysine 4 |
H3K4me1 | Histone 3 Lysine 4 Monomethylation |
H3K4me1/2/3 | Histone 3 Lysine 4 Mono-/Di-/Trimethylation |
H3K4me2/3 | Histone 3 Lysine 4 Di-/Trimethylation |
H3K4me3 | Histone 3 Lysine 4 Trimethylation |
H3K9ac | Histone 3 Lysine 9 Acetylation |
H3K9 | Histone 3 Lysine 9 |
H3K9me1 | Histone 3 Lysine 9 Monomethylation |
H3K9me1/2 | Histone 3 Lysine 9 Mono-/Dimethylation |
H3K9me1/2/3 | Histone 3 Lysine 9 Mono-/Di-/Trimethylation |
H3K9me1/3 | Histone 3 Lysine 9 Mono-/Trimethylation |
H3K9me2 | Histone 3 Lysine 9 Dimethylation |
H3K9me2/3 | Histone 3 Lysine 9 Dimethylation/Trimethylation |
H3K9me3 | Histone 3 Lysine 9 Trimethylation |
H3K9ac | Histone 3 Lysine 9 Acetylation |
H3R17me2 | Histone 3 Arginine 17 Dimethylation |
H3R26me2 | Histone 3 Arginine 26 Dimethylation |
H3R2me1/2 | Histone 3 Arginine 2 Monomethylation/Dimethylation |
H3R2me1/2 | Histone 3 Arginine 2 Monomethylation/Dimethylation |
H3R2me2 | Histone 3 Arginine 2 Dimethylation |
H3R42me2 | Histone 3 Arginine 42 Dimethylation |
H3R8me2 | Histone 3 Arginine 8 Dimethylation |
H4K20 | Histone 4 Lysine 20 |
H4K20me1 | Histone 4 Lysine 20 Monomethylation |
H4K20me1/2 | Histone 4 Lysine 20 Monomethylation/Dimethylation |
H4K20me2/3 | Histone 4 Lysine 20 Dimethylation/Trimethylation |
H4K20me3 | Histone 4 Lysine 20 Trimethylation |
H4K5 | Histone 4 Lysine 5 Methylation |
H4R17me1 | Histone 4 Arginine 17 Monomethylation |
H4R19me1 | Histone 4 Arginine 19 Monomethylation |
H4R3me1 | Histone 4 Arginine 3 Monomethylation |
H4R3me2 | Histone 4 Arginine 3 Dimethylation |
H4 | Histone 4 |
HCFC1 | Host Cell Factor C1 |
H | Healthy |
IFN-γ | Interferon Gamma |
IL-17A | Interleukin 17A |
IL-23 | Interleukin 23 |
IRF3 | Interferon Regulatory Factor 3 |
JARID2 | Jumonji And AT-Rich Interaction Domain Containing 2 |
K6 | K6 Keratin |
K16 | K16 Keratin |
KDM6A | Lysine-specific Demethylase 6A |
KMT2A | Lysine Methyltransferase 2A |
KMT2B | Lysine Methyltransferase 2B |
KMT2C | Lysine Methyltransferase 2C |
KMT2D | Lysine Methyltransferase 2D |
L | Lesional |
LCOR | Ligand-Dependent Nuclear Receptor Corepressor |
LCORL | Ligand-Dependent Nuclear Receptor Corepressor Like |
MAPK | Mitogen-activated protein kinase |
MECOM | MDS1 and EVI1 Complex Locus |
MEN1 | Menin 1 |
MEP50 | WD Repeat Domain 77 |
METTL13 | Methyltransferase 13, EEF1A N-Terminus And K55 |
METTL21A | Methyltransferase 21A, HSPA Lysine |
METTL21C | Methyltransferase 21C, AARS1 Lysine |
METTL22 | Methyltransferase 22, Kin17 Lysine |
MHC-II | Major Histocompatibility Complex Class II |
MLL1 | Lysine Methyltransferase 2A |
MLL2 | Lysine Methyltransferase 2B |
MLL3 | Lysine Methyltransferase 2C |
MLL4 | Lysine Methyltransferase 2D |
mRNA | Messenger Ribonucleic Acid |
Mtase | Methyltransferases |
MTF2 | Metal Response Element Binding Transcription Factor 2 |
N6AMT1 | N-6 Adenine-Specific DNA Methyltransferase 1 |
NCOA6 | Nuclear Receptor Coactivator 6 |
NF-κB | Nuclear Factor Kappa B |
NL | Non-leional/uninvolved |
NSD1 | Nuclear Receptor Binding SET Domain Protein 1 |
NSD2 | Nuclear Receptor Binding SET Domain Protein 2 |
NSD3 | Nuclear Receptor Binding SET Domain Protein 3 |
N-WASP | Neural Wiskott-Aldrich Syndrome Protein (WASP Like Actin Nucleation Promoting Factor) |
PAGR1 | PAXIP1 Associated Glutamate Rich Protein 1 |
PASI | Psoriasis Area and Severity Index |
PAXIP1 | PAX Interacting Protein 1 |
PHF1 | PHD Finger Protein 1 |
PHF19 | PHD Finger Protein 19 |
PRC2 | Polycomb Repressive Complex 2 |
PRDM1 | PR/SET Domain 1 |
PRDM10 | PR/SET Domain 10 |
PRDM11 | PR/SET Domain 11 |
PRDM12 | PR/SET Domain 12 |
PRDM13 | PR/SET Domain 13 |
PRDM14 | PR/SET Domain 14 |
PRDM15 | PR/SET Domain 15 |
PRDM16 | PR/SET Domain 16 |
PRDM2 | PR/SET Domain 2 |
PRDM4 | PR/SET Domain 4 |
PRDM5 | PR/SET Domain 5 |
PRDM6 | PR/SET Domain 6 |
PRDM7 | PR/SET Domain 7 |
PRDM8 | PR/SET Domain 8 |
PRDM9 | PR/SET Domain 9 |
PRMT1 | Protein Arginine Methyltransferase 1 |
PRMT2 | Protein Arginine Methyltransferase 2 |
PRMT3 | Protein Arginine Methyltransferase 3 |
PRMT4 | Protein Arginine Methyltransferase 4 |
PRMT5 | Protein Arginine Methyltransferase 5 |
PRMT6 | Protein Arginine Methyltransferase 6 |
PRMT7 | Protein Arginine Methyltransferase 7 |
PRMT8 | Protein Arginine Methyltransferase 8 |
PRMT9 | Protein Arginine Methyltransferase 9 |
RBBP4 | Retinoblastoma Binding Protein 4, Chromatin Remodeling Factor |
RBBP5 | Retinoblastoma Binding Protein 5, Histone Lysine Methyltransferase Complex Subunit |
RBBP7 | Retinoblastoma Binding Protein 7, Chromatin Remodeling Factor |
RelA | RELA Proto-Oncogene, NF-KB Subunit |
RNA | Ribonucleic Acid |
SET-domain | Suppressor of variegation 3–9, Enhancer of zeste, and Trithorax |
SETD3 | SET Domain Containing 3, Actin N3(Tau)-Histidine Methyltransferase |
SETD4 | SET Domain Containing 4 |
SETD5 | SET Domain Containing 5 |
SETD6 | SET Domain Containing 6, Protein Lysine Methyltransferase |
SETD1A | SET Domain Containing 1A, Histone Lysine Methyltransferase |
SETD1B | SET Domain Containing 1B, Histone Lysine Methyltransferase |
SETD2 | SET Domain Containing 2, Histone Lysine Methyltransferase |
SETD7 | SET Domain Containing Lysine Methyltransferase 7 |
SETD8 | Lysine Methyltransferase 5A (SET Domain Containing Lysine Methyltransferase 8) |
SETDB1 | SET Domain Bifurcated Histone Lysine Methyltransferase 1 |
SETDB2 | SET Domain Bifurcated Histone Lysine Methyltransferase 2 |
SMYD1 | SET and MYND Domain Containing 1 |
SMYD2 | SET and MYND Domain Containing 2 |
SMYD3 | SET and MYND Domain Containing 3 |
SMYD4 | SET and MYND Domain Containing 4 |
SMYD5 | SMYD Family Member 5 |
SRA | Sequence Read Archive |
SUV39H1 | SUV39H1 Histone Lysine Methyltransferase (Suppressor of Variegation 3-9 Homolog 1) |
SUV39H2 | SUV39H2 Histone Lysine Methyltransferase (Suppressor of Variegation 3-9 Homolog 2) |
SUV420H1 | Lysine Methyltransferase 5B (Suppressor of Variegation 4-20 Homolog 1) |
SUV420H2 | Lysine Methyltransferase 5C (Suppressor of Variegation 4-20 Homolog 2) |
SUZ12 | SUZ12 Polycomb Repressive Complex 2 Subunit |
Th1 | T Helper Type 1 |
Th17 | T Helper Type 17 |
Th2 | T Helper Type 2 |
TLR | Toll-like Receptor |
TLR4 | Toll-like Receptor 4 |
TMM | trimmed mean of M-values |
TNF | Tumor Necrosis Factor |
TNFα | Tumor Necrosis Factor Alpha |
TPM | Transcripts Per Million |
Treg | Regulatory T cell |
VCPKMT | Valosin Containing Protein Lysine Methyltransferase |
WDR5 | WD Repeat Domain 5 |
WDR82 | WD Repeat Domain 82 |
WNT10B | Wnt Family Member 10B (Wingless-type MMTV Integration Site Family, Member 10B) |
ZFPM1 | Zinc Finger Protein, FOG Family Member 1 |
ZFPM2 | Zinc Finger Protein, FOG Family Member 2 |
ZNF408 | Zinc Finger Protein 408 |
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Transcriptional Alterations in SET Domain Lysine Methyltransferases in Psoriasis | |||||
---|---|---|---|---|---|
Subfamily | Gene ID | Alternative Name | Histone Modification | Reference | Differentially Expressed |
EZ subfamily | EZH1 | KMT6B | H3K27me1/2/3 | [26,27] | L vs. H |
EZH2 | KMT6A | L vs. H | |||
SET1 subfamily | MLL1 | KMT2A | H3K4me2/3 | [28] | - |
MLL2 | KMT2B | - | |||
MLL3 | KMT2C | H3K4me1 | - | ||
MLL4 | KMT2D | - | |||
SETD1A | KMT2E | H3K4me2/3 | - | ||
SETD1B | KMT2F | - | |||
SET2 subfamily | ASH1L | KMT2H | H3K36me1/2 | [29] | NL vs. H; L vs. H |
NSD1 | KMT3B | H3K36me2 | [30] | L vs. H | |
NSD2 | KMT3G | [30,31] | L vs. H | ||
NSD3 | KMT3F | [30] | L vs. H | ||
SETD2 | KMT3A | H3K36me3 | [32] | L vs. H | |
SMYD subfamily | SMYD1 | KMT3D | Unknown | Unknown | - |
SMYD2 | KMT3C | H3K36me2 | [33] | - | |
SMYD3 | KMT3E | H4K5; H4K20me3 | [34,35] | - | |
SMYD4 | - | Unknown | Unknown | - | |
SMYD5 | - | H4K20me3; H3K36me1; H3K37me1 | [36,37] | - | |
SUV39H subfamily | EHMT1 | KMT1D | H3K9me1/2 | [38] | NL vs. H |
EHMT2 | KMT1C | [38,39] | NL vs. H | ||
SETDB1 | KMT1E | H3K9me1/2/3 | [40,41,42] | - | |
SETDB2 | KMT1F | H3K9me3 | [43] | L vs. H | |
SUV39H1 | KMT1A | H3K9me2/3 | [44,45,46] | - | |
SUV39H2 | KMT1B | L vs. H | |||
SUV4-20 subfamily | SUV420H1 | KMT5B | H4K20me2/3 | [47,48] | NL vs. H; L vs. H |
SUV420H2 | KMT5C | - | |||
Others | SETD7 | KMT7 | H3K4me1 | [49] | - |
SETD8 | KMT5A | H4K20me1 | [50,51] | L vs. H | |
RIZ (PRDM) subfamily (PR/SET domain) | PRDM1 | BLIMP1 | pseudo-MTase | [52] | L vs. H |
PRDM2 | KMT8A | H3K9me2 | [52,53,54] | L vs. H | |
MECOM | KMT8E | Unclear (H3K9me1) | [52,55] | L vs. H | |
PRDM4 | PFM1 | Unknown | Unknown | - | |
PRDM5 | PFM2 | pseudo-Mtase | [52] | - | |
PRDM6 | KMT8C | L vs. H | |||
PRDM7 | ZNF910 | H3K4me3 | [52,56] | - | |
PRDM8 | KMT8D | Unclear (H3K9) | [52,57] | L vs. H | |
PRDM9 | KMT8B | H3K4me1/2/3; H3K9me1/3; H3K18me1; H3K36me3; H4K20me1/2 | [52,58,59,60,61,62] | - | |
PRDM10 | PFM7 | pseudo-MTase | [52] | NL vs. H; L vs. H | |
PRDM11 | PFM8 | Unknown | Unknown | - | |
PRDM12 | PFM9 | pseudo-MTase | [52] | - | |
PRDM13 | PFM10 | Unknown | Unknown | - | |
PRDM14 | PFM11 | pseudo-MTase | [52] | - | |
PRDM15 | ZNF297 | - | |||
PRDM16 | KMT8F | Unclear (H3K9me1; H3K4me3) | [52,55,63] | - | |
ZNF408 | PRDM17 | Unknown | Unknown | - | |
ZFPM1 | FOG1 | - | |||
ZFPM2 | FOG2 | NL vs. H |
MTase Complex | Subtypes of Complex | Gene ID | Alternative Name | Differentially Expressed | |
---|---|---|---|---|---|
PRC2 complex (EZ subfamily) | Core components of PRC2 complex | EED | HEED | NL vs. H; L vs. H | |
EZH1 | KMT6B | L vs. H | |||
EZH2 | KMT6A | L vs. H | |||
SUZ12 | JJAZ1 | - | |||
RBBP4 | RbAp48 | NL vs. H; L vs. H | |||
RBBP7 | RbAp46 | - | |||
PRC2.1 | PRC2.1 | MTF2 | PCL2 | NL vs. H | |
PHF1 | PCL1 | NL vs. H | |||
PHF19 | PCL3 | L vs. H | |||
EPOP-PRC2.1 | EPOP | C17orf96 | L vs. H | ||
PALI1/2-PRC2.1 | LCOR | C10orf12 | - | ||
LCORL | MLR1 | - | |||
PRC2.2 | AEBP2-PRC2.2 | AEBP2 | - | - | |
JARID2-PRC2.2 | JARID2 | JMJ | - | ||
COMPASS- and COMPASS-like complex (SET1 subfamily) | Core components of COMPASS and COMPASS-like complex | ASH2L | ASH2L1 | NL vs. H; L vs. H | |
DPY30 | HDPY-30 | - | |||
RBBP5 | SWD1 | - | |||
WDR5 | SWD3 | - | |||
COMPASS complex | CXXC1 | PHF18 | NL vs. H | ||
HCFC1 | HFC1 | - | |||
SETD1A | KMT2F | - | |||
SETD1B | KMT2G | - | |||
WDR82 | TMEM113 | - | |||
COMPASS-like complex (MLL1/2) | HCFC1 | HFC1 | - | ||
KMT2A | MLL1 | - | |||
KMT2B | MLL2 | - | |||
MEN1 | MENIN | L vs. H | |||
COMPASS-like complex (MLL3/4) | KDM6A | UTX | L vs. H | ||
KMT2C | MLL3 | - | |||
KMT2D | MLL4 | - | |||
NCOA6 | RAP250 | - | |||
PAGR1 | C16orf53 | - | |||
PAXIP1 | PAXIP1L | - |
Transcriptional Alterations in 7β-Strand Lysine Methyltransferases in Psoriasis | ||||||
---|---|---|---|---|---|---|
Group | Gene ID | Alternative Name | Substrate | Modification | Signaling Regulation | Differentially Expressed |
Archaeal KMT-like | ANTKMT | FAM173A | ANT1/2 | K52me3 | Mitochondrial metabolism | - |
ATPSCKMT | FAM173B | ATP synthase c-subunit | K43me3 | - | ||
Eef1a-KMT group | CSKMT | METTL12 | Citrate synthase | K368me1/2/3 or K395me1/2/3 | Mitochondrial metabolism | L vs. H |
EEF1AKMT2 | METTL10 | eEF1A | K318me3 | mRNA translation | - | |
EEF1AKMT4 | ECE2 | eEF1A | K36me2/3 | - | ||
METTL13 | EEF1AKNMT | eEF1A | K55me2 | NL vs. H | ||
Mtase family 16 | CAMKMT | C2orf34 | Calmodulin | K115me3 | Neural development | - |
EEF1AKMT3 | METTL21B | eEF1A | K165me1/2/3 | mRNA translation | - | |
EEF2KMT | FAM86A | eEF2 | K525me3 | L vs. H | ||
ETFBKMT | METTL20 | ETFβ | K200me2/3; K203me2/3 | Mitochondrial metabolism | - | |
METTL21A | FAM119A | HSPA1; HSPA5; HSPA8 | K561me3; K585me3; K565me3 | Chaperones/protein stability | NL vs. H; L vs. H | |
METTL21C | C13orf39 | HSPA8; VCP/p97 | K561me3; K315me3 | - | ||
METTL22 | C16orf68 | KIN17 | K135me3 | Chromatin regulation | - | |
VCPKMT | METTL21D | VCP/p97 | K315me3 | Chaperones/protein stability | L vs. H | |
Others | DOT1L | KMT4 | Histone H3 | K79me1/2/3 | Chromatin regulation | L vs. H |
EEF1AKMT1 | N6AMT2 | eEF1A | K79me3 | mRNA translation | - | |
N6AMT1 | KMT9 | Histone H4 | K12me1 | Chromatin regulation | - |
Types of PRMTs | Gene ID | Alternative Name | Histone Modification | Differentially Expressed |
---|---|---|---|---|
Type I. | PRMT1 | HRMT1L2 | H2AR3me2; H2AR11me2; H4R3me2 | L vs. H |
PRMT2 | HRMT1L1 | H3R8me2 | L vs. H | |
PRMT3 | HRMT1L3 | H4R3me2 | - | |
PRMT4 | CARM1 | H3R2me2; H3R17me2; H3R26me2; H3R42me2 | L vs. H | |
PRMT6 | HRMT1L6 | H2AR3me2; H2AR11me2; H2AR29me2; H3R2me2; H3R42me2; H4R3me2 | - | |
PRMT8 | HRMT1L3 | H4R3me2 | - | |
Type II. | PRMT5 | HRMT1L5 | H2AR3me1/2; H3R2me1/2; H3R8me2; H4R3me2 | NL vs. H; L vs. H |
PRMT9 | PRMT10 | - | - | |
Type III. | PRMT7 | KIAA1933 | H2AR3me1; H2BR29me1; H2BR31me1; H2BR33me1; H3R2me1/2; H4R3me1; H4R17me1; H4R19me1 | L vs. H |
Subfamily | Gene ID | Transcript ID | Transcript Type | log2fc L vs. H | FDR L vs. H | log2fc NL vs. H | FDR NL vs. H | Uniprot Protein ID |
---|---|---|---|---|---|---|---|---|
EZ subfamily | EZH1 | ENST00000585550.5 | Retained intron | −1.165 | 4.17 × 10−2 | 0.606 | 5.39 × 10−1 | - |
EZH2 | ENST00000320356.6 | Protein-coding | 2.625 | 1.73 × 10−5 | 0.773 | 5.94 × 10−1 | Q15910-2 | |
ENST00000460911.5 | 2.342 | 6.71 × 10−11 | 0.166 | 8.70 × 10−1 | Q15910-1 | |||
ENST00000350995.6 | 2.050 | 1.58 × 10−4 | 0.172 | 9.12 × 10−1 | Q15910-3 | |||
ENST00000483967.5 | 1.239 | 9.00 × 10−3 | −0.627 | 5.79 × 10−1 | Q15910-4 | |||
SET2 subfamily | ASH1L | ENST00000492987.2 | Nonsense-mediated decay | −1.342 | 8.29 × 10−6 | 0.837 | 4.52 × 10−3 | H0YI82 |
NSD1 | ENST00000347982.8 | Protein-coding | 5.601 | 1.18 × 10−6 | −0.485 | 9.06 × 10−1 | A0A8I5QJP2 | |
NSD2 | ENST00000508803.5 | Protein-coding | 3.598 | 2.25 × 10−9 | −0.222 | 9.09 × 10−1 | O96028-1 | |
ENST00000482415.6 | Processed transcript | 2.818 | 1.91 × 10−6 | 0.902 | 4.90 × 10−1 | |||
NSD3 | ENST00000525081.1 | Processed transcript | −1.255 | 3.37 × 10−9 | 0.046 | 9.18 × 10−1 | - | |
SETD2 | ENST00000330022.11 | Nonsense-mediated decay | −1.442 | 6.93 × 10−3 | 0.424 | 6.10 × 10−1 | H7BXT4 | |
SUV39 subfamily | EHMT1 | ENST00000640639.1 | Protein-coding | −0.816 | 2.68 × 10−1 | 1.989 | 1.81 × 10−2 | A0A1W2PPZ7 |
EHMT1 | ENST00000488242.2 | Processed transcript | −0.158 | 6.96 × 10−1 | 1.108 | 9.57 × 10−3 | - | |
EHMT2 | ENST00000477678.1 | Retained intron | −0.855 | 8.12 × 10−2 | 1.906 | 5.07 × 10−6 | - | |
SETDB2 | ENST00000317257.12 | Protein-coding | −1.932 | 4.00 × 10−2 | −0.997 | 5.13 × 10−1 | Q96T68-2 | |
SUV39H2 | ENST00000354919.10 | Protein-coding | 1.715 | 1.89 × 10−7 | −0.304 | 7.42 × 10−1 | Q9H5I1-1 | |
SUV39H2 | ENST00000358298.6 | 1.236 | 3.74 × 10−2 | 0.594 | 6.19 × 10−1 | H0Y306 | ||
SUV4-20 subfamily | SUV420H1 (KMT5B) | ENST00000615954.4 | Protein-coding | 1.715 | 2.63 × 10−2 | −0.027 | 9.92 × 10−1 | Q4FZB7-1 |
ENST00000405515.5 | −0.080 | 9.30 × 10−1 | 1.985 | 6.14 × 10−3 | Q4FZB7-2 | |||
Others | SETD8 (KMT5A) | ENST00000437502.1 | Protein-coding | 1.025 | 1.81 × 10−2 | −0.914 | 3.44 × 10−1 | C9JKQ0 |
RIZ (PRDM) subfamily (PR/SET domain) | PRDM1 | ENST00000369091.6 | Protein-coding | 3.995 | 1.94 × 10−4 | 1.265 | 5.76 × 10−1 | O75626-2 |
ENST00000369096.8 | 1.745 | 9.12 × 10−40 | −0.023 | 9.34 × 10−1 | O75626-1 | |||
PRDM2 | ENST00000491134.5 | Nonsense-mediated decay | 1.778 | 5.48 × 10−5 | −0.080 | 9.51 × 10−1 | H0Y9J3 | |
MECOM | ENST00000628990.2 | Protein-coding | 1.182 | 3.70 × 10−3 | −0.375 | 7.08 × 10−1 | Q03112-1 | |
PRDM6 | ENST00000407847.4 | Protein-coding | −1.334 | 4.97 × 10−19 | −0.104 | 6.59 × 10−1 | Q9NQX0-3 | |
PRDM8 | ENST00000339711.8 | Protein-coding | −2.606 | 1.18 × 10−4 | −0.943 | 4.30 × 10−1 | Q9NQV8-1 | |
PRDM10 | ENST00000528746.5 | Protein-coding | 1.640 | 1.60 × 10−2 | −0.342 | 8.43 × 10−1 | E9PLV1 | |
ENST00000423662.6 | −1.914 | 1.55 × 10−2 | 1.407 | 9.96 × 10−2 | Q9NQV6-1 | |||
ZFPM2 | ENST00000517361.1 | Protein-coding | −0.238 | 7.03 × 10−1 | 1.213 | 4.54 × 10−2 | E7ET52 |
Subfamily | Gene | Modulatory Role | Known Relevance to Psoriasis | Potential Relevance to Psoriasis |
---|---|---|---|---|
EZ subfamily | EZH2 | Promotes keratinocyte proliferation and inflammation; downregulates miR-125a-5p, affecting TGFβ/SMAD pathway [15,76] | Drives keratinocyte hyperproliferation and inflammatory response in psoriatic skin [15,76] | - |
SET2 subfamily | ASH1L | Modulates c-Myc activation and NF-κB signaling [77,78] | - | Affects keratinocyte proliferation/differentiation balance; suppresses TLR-induced TRAF6/NF-κB signaling modulating IL–17–mediated inflammation [79,80] |
NSD1 | Modulates NF-κB via p65 methylation [81]; regulates proliferation via Wnt10b [82] | NF-κB is a key regulator of psoriatic inflammation [80]; altered expression of Wnt10b affects keratinocyte proliferation and cell migration [83] | ||
NSD2 | Modulates Wnt/cyclin D1 pathway [84] | Elevated Cyclin D1 level contributes to hyperproliferation [85] | ||
SETD2 | Regulates Th17/Treg via Lpcat4 [86], and AKT/mTOR signaling during wound healing [87] | Aberrant activation of mTORC1 signaling promoted hyperproliferation [88]; accelerated wound healing [89]; elevated Th17/Treg ratio [90] | ||
SUV39 subfamily | EHMT1 | Regulates cytokine expression via p50 [91]; modulates Treg function via FOXP3 [92] | - | NF-κB is a key regulator of psoriatic inflammation [80]; FOXP3-mediated Treg deficiency and excessive inflammation [93,94] |
SETDB2 | Regulates mitosis [43]; IFN-I response in macrophages [95] | Regulation of keratinocyte proliferation, and M1/M2 macrophage imbalance [96] | ||
SUV39H2 | Maintains basal keratinocyte stemness [97] | Keratinocyte proliferation, differentiation, and barrier formation and function [88,98,99] | ||
SUV4-20 subfamily | SUV420H1 | Controls DNA replication, telomere, and genome stability [100,101,102] | - | Keratinocyte proliferation and telomeric abnormalities [103] |
Other SET domain-containing histone lysine methyltransferases | SETD8 | Regulates cell proliferation and differentiation via p53, p63, and c-Myc [104] | - | Keratinocyte proliferation, differentiation, and barrier formation and function [88,98,99] |
RIZ (PRDM) subfamily (PR/SET domain) | MECOM | Regulates cell proliferation [105]; monocyte/macrophage differentiation [106] | Altered MECOM expression correlates with increased keratinocyte proliferation in psoriatic lesions [105] | Increased tissue levels of TNFα⁺ monocytes/macrophages [107] |
PRDM2 | Represses cell cycle genes (e.g., CCNA2) [108]; regulates Th function via GATA3 [109] | - | Increased CCNA2 [110] contribution to keratinocyte hyperproliferation; Th1/Th2 imbalance [111] |
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Romhányi, D.; Bessenyei, Á.; Szabó, K.; Kemény, L.; Gyulai, R.; Groma, G. Unveiling the Role of Histone Methyltransferases in Psoriasis Pathogenesis: Insights from Transcriptomic Analysis. Int. J. Mol. Sci. 2025, 26, 6329. https://doi.org/10.3390/ijms26136329
Romhányi D, Bessenyei Á, Szabó K, Kemény L, Gyulai R, Groma G. Unveiling the Role of Histone Methyltransferases in Psoriasis Pathogenesis: Insights from Transcriptomic Analysis. International Journal of Molecular Sciences. 2025; 26(13):6329. https://doi.org/10.3390/ijms26136329
Chicago/Turabian StyleRomhányi, Dóra, Ágnes Bessenyei, Kornélia Szabó, Lajos Kemény, Rolland Gyulai, and Gergely Groma. 2025. "Unveiling the Role of Histone Methyltransferases in Psoriasis Pathogenesis: Insights from Transcriptomic Analysis" International Journal of Molecular Sciences 26, no. 13: 6329. https://doi.org/10.3390/ijms26136329
APA StyleRomhányi, D., Bessenyei, Á., Szabó, K., Kemény, L., Gyulai, R., & Groma, G. (2025). Unveiling the Role of Histone Methyltransferases in Psoriasis Pathogenesis: Insights from Transcriptomic Analysis. International Journal of Molecular Sciences, 26(13), 6329. https://doi.org/10.3390/ijms26136329