From: Epigenome alterations in aortic valve stenosis and its related left ventricular hypertrophy
Gene name; official gene symbol | Epigenetic function | Expression in stenotic valves and aortic valve cells [reference] |
---|---|---|
AT-rich interaction domain 1A; SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily F Member 1; ARID1A | Chromatin remodeling cofactor | ↑ PAVECs* [177] |
AT-rich interaction domain 4B; ARID4B | HAT cofactor | ↑ HAVICs1 [78] |
AT-rich interaction domain 5B; ARID5B | HDM cofactor (H3K9me2 → H3K9) | ↑ AS [99], ↑HAVICs1 [78], ↑ PAVICs# [178], (NOTH1+/−) ECsa [67] |
Anti-silencing function 1B histone chaperone; ASF1B | Histone (H3/H4) chaperone | |
ASH2 like histone lysine methyltransferase complex subunit; ASH2L | HMT cofactor, component of COMPASS H3K4 methyltransferase complex | HAVECsc [77], ↑ PAVICs# [178], ↓ HAVECs by miR-483p and unidirectional shear stress [179] |
ATRX, chromatin remodeler; ATRX | Chromatin remodeling | ↑ HAVICs1 [78] |
BTG3 associated nuclear protein; BANP | Histone acetylation | HAVECsc [77] |
BRCA1 associated protein 1; BAP1/ KIAA0272 | Deubiquitination (H2AK119ub1 → H2AK119), PcG protein; | ↑ PAVECs* [177] |
BRCA1 Associated RING Domain 1; BARD1 | Histone ubiquitination (H2AX, H2A, H2B, H3, H4 → H2AXub, H2Aub, H2Bub, H3ub, H4ub) | ↓ PAVECs* [177] |
Bromodomain adjacent to zinc finger domain 1A; BAZ1A/ACF1 | Histone chaperone | HAVECsc [77] |
BCL6 corepressor; BCOR | PcG protein | ↑ AS [99] |
BMI1 proto-oncogene, polycomb ring finger; BMI1 | PcG protein | HAVECsb [63] |
Bromodomain containing 1; BRD1 | Histone acetyl-lysine reader | ↓ HAVICs1 [78] |
Bromodomain containing 9; BRD9 | Histone acetyl-lysine reader | ↓ HAVICs1 [78] |
Brain and reproductive organ-expressed; TNFRSF1A modulator; BRE | Histone [H2A(X)] ubiquitination cofactor | |
Bromodomain and PHD finger containing 1; BRPF1 | Histone acetyl-lysine reader, component of the MOZ(KAT6A/MYST3)/MORF(KAT6B/MYST4) HAT complex | |
Bromodomain and WD repeat domain containing 1; BRWD1 | Histone acetyl-lysine reader; chromatin remodeling | ↑ HAVICs1 [78] |
Coactivator associated arginine methyltransferase 1; CARM1/PRMT4 | Histone-Arginine(R) methyltransferase (H3R17 → H3R17me, H3R17me2a) | |
Chromobox 2; CBX2 | Methyl-lysine(K) reader (H3K9me3, H3K27me3), component of PRC1-like complex | (NOTH1+/−) ECsa [67] |
Chromobox 3; CBX3 | Methyl-lysine(K) reader (H3K9me3), epigenetic repressor- interacts with MECP2 and modulates epigenetic gene silencing during myogenic differentiation | ↑ AS [99], cardiomyocytes of AS patients with cardiomyopathy [181] |
Chromobox 4; CBX4 | Methyl-lysine(K) reader (H3K9me3), component of PRC1-like complex | ↑ BAVc vs. TAVn [182] |
Chromobox 7; CBX7 | Methyl-lysine(K) reader (H3K9me3, H3K27me3), component of PRC1-like complex | ↓ HAVICs1 [78] |
Chromobox 8; CBX8 | Methyl-lysine(K) reader (H3K9me3, H3K27me3), component of PRC1-like complex | ↑ BAVc vs. TAVn, ↑ TAVc vs. TAVn [182] |
CECR2, histone acetyl-lysine reader; CECR2 | Histone Acetyl-Lysine(K) reader, component of CERF SWI/SNF chromatin remodeling complex | ↓ AS [99], ↓ BAVc vs. TAVn, ↓ TAVc vs. TAVn [182], ↑ BAVr vs. BAVc [183] |
Chromatin assembly factor 1 subunit A; CHAF1A | Histone chaperone and epigenetic regulator, primary component of CAF1 | HAVECsb [63] |
Chromatin assembly factor 1 subunit B; CHAF1B | Histone chaperone and epigenetic regulator, primary component of CAF1 complex | HAVECsb [63] |
Chromodomain helicase DNA binding protein 1; CHD1 | Chromatin remodeling factor | ↓ PAVECs* [177] |
Chromodomain helicase DNA binding protein 1; CHD1L | Chromatin-remodeling following DNA damage, interacts with poly(ADP-ribose) and catalyzes PARP1-stimulated nucleosome sliding | ↓ HAVICs1 [78] |
Chromodomain helicase DNA binding protein 9; CHD9 | Chromatin related mesenchymal modulator, associates with A/T-rich regulatory regions in promoters of genes that participate in the differentiation of progenitors during osteogenesis | HAVECsc [77] |
CREB binding protein; CREBBP | CREB and its paralog p300 (EP300) constitute the KAT3 family of HATs in mammals | ↑ HAVICs1 [78] |
CXXC finger protein 1; CXXC1 | Binds DNA sequences with unmethylated CpG, epigenetic regulator of both cytosine and histone methylation, component of COMPASS/SETD1A/B HMT complex | ↓ HAVICs1 [78] |
DEK proto-oncogene; DEK | Chromatin remodeling, histone chaperone | ↓ PAVECs* [177] |
Double PHD fingers 3; DPF3 | Histone acetylation and methylation reader of BAF chromatin remodeling complex, recruits BRG1 to genomic targets | |
EMSY, BRCA2 interacting transcriptional repressor; EMSY /C11orf30 | Histone methylation cofactor, part of EMSY/KDM5A/SIN3B HMT complex | ↓ PAVICs# [178] |
Enhancer of polycomb homolog 1; EPC1 | PcG protein, component of the NUA4 HAT complex | ↑ PAVECs* [177] |
Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit; EZH2 /KMT6 | PcG protein, Histone methylation (H3K27 → H3K27me1, H3K27me2, H3K27me3) | ↓ PAVECs* [177] |
EYA transcriptional coactivator and phosphatase 1; EYA1 | Dephosphorylation of Tyr(Y)-142 in H2AX (H2AXY142ph) | |
EYA transcriptional coactivator and phosphatase 4; EYA4 | Dephosphorylation of Tyr(Y)-142 in H2AX (H2AXY142ph) | |
Histone deacetylase 1; HDAC1 | Class I HDAC member | |
Histone deacetylase 3; HDAC3 | Class I HDAC member | ↓ HAVICs1 [78] |
Histone deacetylase 5; HDAC5 | Class II HDAC member | |
Histone deacetylase 7; HDAC7 | Class IIa HDAC member | ↓ HAVICs1 [78] |
Histone deacetylase 9; HDAC9 | Class II HDAC member | ↓ HAVICs1 [78] |
Histone cell cycle regulator; HIRA | Histone chaperone, cooperates with ASF1A to promote replication-independent chromatin assembly, required for early steps of osteoblastic differentiation, interacts with OGT and regulates nucleosome assembly and cellular senescence. | |
Helicase like transcription factor; SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily A, Member 3; HLTF | Chromatin remodeling cofactor, member of the SWI/SNF family, acts as a ubiquitin ligase for ‘Lys-63’-linked polyubiquitination of chromatin-bound PCNA. | Blood dried spots- congenital AS [42] |
IKAROS family zinc finger 1; IKZF1 | Chromatin remodeling | ↑ BAVc vs. TAVn, ↑ TAVc vs. TAVn [182] |
Inhibitor of growth family member 3; ING3 | Chromatin remodeling, HAT cofactor, component of the NUA4 HAT complex, binds H3K4me3 histone marks | |
INO80 complex subunit C; INO80C | Chromatin remodeling cofactor, component of the INO80 chromatin remodeling complex | ↑ HAVICs1 [78] |
Janus Kinase 2; JAK2 | Phosphorylation of Tyr(Y)-41 of histone H3 (H3T41 → H3Y41ph) | ↑ rat AVICs*** [64] |
Jade family PHD finger 1; JADE1 /PHF17 | Histone acetylation (H3, H4 → H3ac, H4ac), component of HBO1 HAT complex | ↓ AS [99] |
Jade Family PHD Finger 2; JADE2 | Histone acetylation (H3, H4 → H3ac, H4ac), component of HBO1 HAT complex | HAVECsc [77] |
Arginine demethylase and lysine hydroxylase; JMJD6 | Histone arginine demethylase (H3R2me, H4R3me → H3R2, H4R3) and a lysyl-hydroxylase. | ↑ PAVICs# [178] |
Lysine acetyltransferase 2A; KAT2A /GCN5 | HAT | |
Lysine acetyltransferase 2B; KAT2B | HAT | |
Lysine acetyltransferase 6A; KAT6A /MYST3 | HAT (H3, H4 → H3ac, H4ac), component of MOZ/MORF HAT complex | ↓ PAVECs* [177] |
Lysine acetyltransferase 7; KAT7 /HBOA/MYST2 | HAT (H4 → H4ac), component of HBO1 HAT complex | ↓ PAVECs* [177] |
Lysine acetyltransferase 8; KAT8 /MYST1/MOF | HAT (H2A, H3, H4 → H2Aac, H3ac, H4ac), member of the MYST HAT family | HAVECsb [63] |
Lysine demethylase 1A; KDM1A / KIAA0601 | Histone demethylase (H3K4me1, H3K4me2, H3K9me → H3K4, H3K9), component of NuRD complex | ↓ PAVECs* [177] |
Lysine demethylase 3A; KDM3A/ JMJD1 | Histone demethylase (H3K9me1, H3K9me2 → H3K9) | HAVECsb [63] |
Lysine demethylase 5C; KDM5C /Xe169/ JARID1C | Histone demethylase (H3K4me3 → H3K4me2, H3K4me1) | |
Lysine demethylase 6B; KDM6B /JMJD3 | Histone demethylases (H3K27me2. H3K27me4 → H3K28), promotes osteogenic differentiation of human MSCs, regulates osteoblast differentiation via transcription factors RUNX2 and SP/OSX | ↑ PAVICs# [178] |
Lysine demethylase 7A; KDM7A /JHDM1D | Histone demethylase (H3K9me2, H3K27me2, H4K20me1 → H3K9, H3K27, H4K20) | HAVECsb [63] |
Lysine methyltransferase 2A; KMT2A /MLL | HMT (H3K4 → H3K4me), catalytic subunit of MLL1/MLL complex | |
Lysine methyltransferase 2B; KMT2B /KIAA0304 | HMT (H3K4 → H3K4me3) | ↓ PAVECs* [177] |
Lysine methyltransferase 2E; KMT2E | HMT (H3K4 → H3K4me1, H3K4me2) | ↓ PAVICs# [178] |
L(3)Mbt-Like 3 (Drosophila); L3MBTL3 /KIAA1798 | Methyl-lysine(K) reader (H4K20me), putative PcG protein | |
Lysyl oxidase like 2; LOXL2 | Counteracts HMTs, acts as H3K4me2/3 deaminase, thus giving cells an additional method for removing methylated residues | |
Leucine rich repeats and WD repeat domain containing 1; LRWD1 | Chromatin remodeling, binds H3K9me3, H3K20me3 and H4K27me3 in a cooperative manner with DNA methylation | ↓ HAVICs1 [78] |
MYC associated factor X; MAX | Histone modification write cofactor involved in histone methylation and acetylation, epigenetic sensor of 5-carboxylcytosine | |
Microspherule protein 1; MCRS1 | Putative regulatory component of INO80 chromatin remodeling complex with HAT activity (H4K5, H4K8, H4K16 → H4K5ac, H4K8ac, H4K16ac) | |
Megakaryoblastic Leukemia (Translocation); MKL1/ MRTFA | Epigenetic orchestrator that connects chromatin and histone modification to: oxidative stress and oxLDL-induced endothelial injury, LPS and endothelin induced proinflammatory gene expression in macrophages and VSMCs, correspondingly; expression of SMC differentiation markers; TGFβ-induced fibrogenesis; cardiac hypertrophy | ↑ AS [184] |
Nucleosome assembly protein 1 like 2; NAP1L2 | Histone modification cofactor; associated with histone H3 and H4 acetylation involved in nucleosome assembly and exchange of H2A-H2B dimmers | HAVECsb [63], ↓ AS [88], ↓ BAVc vs. TAVn, ↓ TAVc vs. TAVn [182] |
Nuclear autoantigenic sperm protein; NASP | Histone chaperone, chromatin remodeling | |
Nuclear receptor corepressor 2; NCOR2 | Histone acetylation eraser | |
O-linked N-acetylglucosamine; GlcNAc transferase; OGT | O-GlcNAc transferase, PcG protein, modifies members of the TET family | HAVECsc [77], ↑ HAVICs1 [78], ↑ PAVECs* [177], LV tissue from AS patients [185], ↓ HAVECs by miRNA-181b and oscillatory shear stress [186] |
Poly; ADP-ribose polymerase 1; PARP1 | Chromatin remodeling; Histone H1 poly[ADP]-ribosylation, modulates chromatin architecture in a context-dependent manner, controls epigenetic modifications of both histones and DNA, poly(ADP-ribosyl)ation (PARylation)--participates in the establishment and maintenance of a genome methylation pattern | ↑ PAVECs vs. PAEC* [177], ↑ TAVc vs. BAVc, leukotriene C4(LTC4) treated VICs [187] |
PAX3 and PAX7 binding protein 1; PAXBP1 /C21orf66 | Adapter protein linking the transcription factors PAX3 and PAX7 to the histone methylation machinery, involved in myogenesis. | |
PAX interacting protein 1; PAXIP1 | HMT cofactor (H3K4 → H3K4me3), subunit of the MLL3/MLL4 HMT complex | ↓ PAVECs* [177] |
Polycomb group ring finger 2; PCGF2 /MEL18 | PcG protein, component of PRC1-like complex | ↑ PAVECs* [177] |
Polycomb group ring finger 5; PCGF5 | PcG protein, component of PRC1-like complex | ↑ AS [114] |
PHD finger protein 1; PHF1 | PcG protein, component of PRC2 complex | |
PHD finger protein 2; Jumonji C domain-containing histone demethylase 1E; PHF2 /GRC5 | Lysine(K) demethylase (H3K9me2 → H3K9), component of PKA-dependent PHF2-ARID5B HDM complex | ↑ PAVECs vs. PAECs*$ [177] |
PHD finger protein 19; PHF19 | PcG protein, chromatin remodeling, HAT cofactor, binds H3K36me3 and recruits the PRC2 complex | ↓ HAVICs1 [78] |
Protein Kinase N1; PKN1 | Histone phosphorylation at threonine(T)11 (H3T11 → H3T11ph) | ↓ HAVICs1 [78] |
PR/SET domain 1; PRDM1 | HMT cofactor (H3K9 → H3K9me), lack intrinsic HMT activity, but instead recruits G9A/EHMT2/H3K9 HMT | HAVECsb [63], (NOTH1+/−) ECsa [67], HAVECsc [77], ↑ HAVICs1 [78] |
PR/SET domain 4; PRDM4 | Histone arginine methylation (H4R3 → H4R3me2s) | ↓ PAVECs* [177] |
PR/SET domain 6; PRDM6 /PRISM | HMT cofactor (H3R2, H4K20 H3R2me1, H3R2me2, H4K20me1), acts as a transcriptional repressor of VSMCs gene expression, lack intrinsic HMT activity, but instead recruits G9A/EHMT2/H3K9 HMT | ↓ PAVICs** [180] |
PR/SET domain 8; PRDM8 | HMT preferentially acting on H3K9 | HAVECsb [63] |
Protein arginine methyltransferase 1; PRMT1 | Arginine(R) methyltransferase (H4R3 → H4R3me1, H4R3me2a), participate in reading of repressive DNA methylation marks | |
Protein arginine methyltransferase 5; PRMT5 | Arginine(R) methyltransferase (H3R8, H4R3 → H3R8me, H4R3me) | ↓ HAVICs1 [78] |
RB binding protein 4, chromatin remodeling factor; RBBP4 | Histone chaperone, part of the Mi-2/NuRD chromatin remodeling complex | |
RB binding protein 5, histone lysine methyltransferase complex subunit; RBBP5 | HMT cofactor (H3K4 → H3K4me1, H3K4me2, H3K4me3), part of the COMPASS and MLL1/MLL complex | ↑ HAVICs1 [78] |
RB transcriptional corepressor like 1; RBL1 | Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression, controls histone H4 Lys-20 trimethylation. | ↓ PAVECs* [177] |
RB transcriptional corepressor like 2; RBL2 | Chromatin remodeling, repression of DNMTs (e.g. DNMT3A, DNMT3B) and control of global DNA methylation, | |
RuvB like AAA ATPase 1; RUVBL1 | Chromatin remodeling, Histone phosphorylation, component of the NuA4 and INO80 complex | |
SAM domain, SH3 domain and nuclear localization signals 1; SAMSN1 | Implicated in the epigenetic control of gene expression, regulates the activity of HDAC1 | |
SATB homeobox 1; SATB1 | Chromatin remodeling cofactor | HAVECsb [63] |
SET domain bifurcated 1; SETDB1 | HAT (H3K9 → H3K9me3 | ↑ PAVICs# [178] |
SET domain and mariner transposase fusion gene; SETMAR | HAT (H3K4, H3K36 → H3K4me, H3K36me) | ↑ HAVICs1 [78] |
SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 1; SMARCAL1 | Chromatin remodeling | |
SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2; SMARCA2 | Chromatin remodeling, histone modification reader (targets H3) | ↑ HAVICs1 [78] |
SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1; SMARCB1 | core subunit of the SWI/SNF (BAF) chromatin-remodeling complex, histone modification reader (targets H3K56) | |
SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 1; SMARCC1 | Chromatin remodeling cofactor | HAVECsc [77] |
SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 2; SMARCC2 | Chromatin remodeling cofactor | ↑ PAVECs* [177] |
SMYD family member 5; SMYD5 | HMT (H4K20 → H4K20me3), part of NCoR complex | ↓ HAVICs1 [78] |
Suppressor of variegation 3–9 homolog 2; SUV39H2 /KMT1B | HAT (H3K9me1 → H3K9me3) | HAVECsb [63] |
Transcriptional adaptor 3; TADA3 | HAT cofactor, component of the PCAF complex | ↓ HAVICs1 [78] |
TATA-box binding protein associated factor 5 like; TAF5L | HAT cofactor, component of the PCAF complex | ↓ HAVICs1 [78] |
Tripartite motif containing 24; TRIM24 | Human chromatin reader, lysine acetylated histone binding | ↑ HAVICs1 [78] |
Tripartite motif containing 28; TRIM28 | Histone modification reader (targets H3) | ↓ HAVICs1 [78] |
Ubinuclein 1; UBN1 | HMT cofactor | HAVECsc [77] |
Ubiquitin protein ligase E3 component n-recognin 2; UBR2 /KIAA0349 | Modification Histone ubiquitination (targets H2A) | ↓ PAVECs* [177] |
Wolf-Hirschhorn syndrome candidate 1; WHSC1 /NSD2 | HMT (H3K27 → H3K27me) | |
Wolf-Hirschhorn syndrome candidate 1-like 1; WHSC1L1 /NSD3 | member of the NSD methyltransferase family (targets H3K4, H3K27) | ↑ HAVICs1 [78] |