Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress
Abstract
:1. Introduction
2. Results
2.1. Identification of Target Genes
2.2. Functional Classification of Genes
2.3. Analysis of Enriched Transcription Factor Binding Sites and Composite Modules
2.4. Finding Master Regulators in Networks
3. Discussion
4. Materials and Methods
4.1. Sample Preparation and Cell Culture Experiments
4.2. Epigenome-Wide DNA Methylation Analysis
4.3. Advanced Bioinformatics Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene Symbol | Gene Description | DiffScore 1 | ECs + Avg_Beta 2 | ECs − Avg_Beta | TargetID 3 | p-Value 4 |
---|---|---|---|---|---|---|
EEF1D | eukaryotic translation elongation factor 1 delta | −109.1854 | 0.6555644 | 0.8999788 | cg22186533 | 1.21 × 10−11 |
MMD | monocyte to macrophage differentiation-associated | −35.18965 | 0.2981108 | 0.5100111 | cg14861570 | 0.000302716 |
TESK1 | testis associated actin remodeling kinase 1 | −31.42026 | 0.4998818 | 0.6956196 | cg09000510 | 0.000721064 |
SLC24A4 | solute carrier family 24 member 4 | −28.64084 | 0.3270859 | 0.5232344 | cg15052901 | 0.001367464 |
MYH3 | myosin heavy chain 3 | −28.24431 | 0.2393593 | 0.4242639 | cg18190433 | 0.001498197 |
PDGFB | platelet derived growth factor subunit B | −24.95273 | 0.11867 | 0.2644652 | cg19167673 | 0.003196885 |
AR | androgen receptor | −24.15009 | 0.5732113 | 0.7435369 | cg27271368 | 0.003845838 |
ZCCHC10 | zinc finger CCHC-type containing 10 | −22.23847 | 0.585928 | 0.748945 | cg08801754 | 0.005972457 |
CELSR3 | cadherin EGF LAG seven-pass G-type receptor 3 | −22.23847 | 0.5043565 | 0.6789438 | cg06621358 | 0.005972457 |
CNIH2 | cornichon family AMPA receptor auxiliary protein 2 | −21.25318 | 0.1661903 | 0.3161516 | cg19026260 | 0.007493453 |
ZFP28 | ZFP28 zinc finger protein | 16.8081 | 0.4203998 | 0.2640518 | cg23850212 | 0.02085403 |
YY1 | YY1 transcription factor | 18.57949 | 0.7956405 | 0.6552107 | cg22763181 | 0.013869187 |
FRMD1 | FERM domain containing 1 | 19.00112 | 0.6587915 | 0.49145 | cg00350478 | 0.012586008 |
MEST | mesoderm specific transcript | 21.27902 | 0.8093046 | 0.6647319 | cg13917504 | 0.007449 |
LARP1 | La ribonucleoprotein 1, translational regulator | 23.04286 | 0.5051906 | 0.3232486 | cg23613317 | 0.004962654 |
CRELD2 | cysteine rich with EGF like domains 2 | 23.1515 | 0.836981 | 0.6953279 | cg25882056 | 0.004840052 |
RAB9A | RAB9A, member RAS oncogene family | 25.78106 | 0.7809207 | 0.6158033 | cg02620228 | 0.002641764 |
KRT17 | keratin 17 | 28.64084 | 0.7502007 | 0.5708218 | cg00214794 | 0.001367464 |
SLC29A1 | solute carrier family 29 member 1 (Augustine blood group) | 45.2453 | 0.7506605 | 0.5342799 | cg10519140 | 2.98862 × 10−5 |
SLC45A1 | solute carrier family 45 member 1 | 57.2597 | 0.6744524 | 0.4233551 | cg11283860 | 1.87945 × 10−6 |
Gene Symbol | Gene Description | DiffScore 1 | SMCs + Avg_Beta 2 | SMCs − Avg_Beta | TargetID 3 | p-Value 4 |
---|---|---|---|---|---|---|
SCT | secretin | −44.15369 | 0.3001944 | 0.5255814 | cg05782292 | 3.84265 × 10−5 |
HLTF | helicase-like transcription factor | −37.04874 | 0.3306479 | 0.5443499 | cg26151310 | 0.0001973 |
CDH2 | cadherin 2 | −34.43425 | 0.3850524 | 0.5944616 | cg09313439 | 0.000360226 |
ZNRF1 | zinc and ring finger 1 | −30.55943 | 0.385322 | 0.5856031 | cg20957193 | 0.000879138 |
PRADC1 | protease associated domain containing 1 | −28.45422 | 0.4262078 | 0.6192294 | cg26993951 | 0.001427506 |
CCNJL | cyclin J-like | −21.76985 | 0.4390145 | 0.6126426 | cg17178888 | 0.006652961 |
METTL25B | methyltransferase-like 25B | −21.18877 | 0.4171189 | 0.590144 | cg23881601 | 0.007605416 |
CDCA5 | cell division cycle-associated 5 | −21.18382 | 0.4315823 | 0.6038101 | cg20252016 | 0.00761409 |
SIRT3 | sirtuin 3 | −20.95826 | 0.7362766 | 0.8588417 | cg23530288 | 0.008019993 |
TCF15 | transcription factor 15 | −20.04535 | 0.3651721 | 0.534321 | cg06143901 | 0.009896121 |
TMEM215 | transmembrane protein 215 | 29.97724 | 0.8431917 | 0.6911527 | cg11308840 | 0.001005254 |
KMT2D | lysine methyltransferase 2D | 30.48615 | 0.4764972 | 0.2821061 | cg24471867 | 0.000894098 |
CDC37L1 | cell division cycle 37-like 1, HSP90 cochaperone | 30.55943 | 0.8350812 | 0.6772436 | cg22189519 | 0.000879138 |
SPA17 | sperm autoantigenic protein 17 | 34.0979 | 0.8123621 | 0.6387361 | cg22318304 | 0.000389233 |
PGBD4 | piggyBac transposable element derived 4 | 35.79305 | 0.6302417 | 0.4193449 | cg12237946 | 0.000263448 |
KHK | ketohexokinase | 39.8873 | 0.8598925 | 0.6937668 | cg01522194 | 0.000102629 |
RNF213 | ring finger protein 213 | 44.15369 | 0.8767144 | 0.7105584 | cg09907395 | 3.84265 × 10−5 |
MRPL12 | mitochondrial ribosomal protein L12 | 48.63778 | 0.816642 | 0.6133671 | cg01372689 | 1.36843 × 10−5 |
RPRM | reprimo, TP53-dependent G2 arrest mediator homolog | 58.14957 | 0.6450388 | 0.3928624 | cg18411898 | 1.53124 × 10−6E |
SLC22A18 | solute carrier family 22 member 18 | 77.42734 | 0.8139806 | 0.5674041 | cg16035277 | 1.80828 × 10−8 |
Gene Symbol | Gene Description | DiffScore 1 | FBs + Avg_Beta 2 | FBs − Avg_Beta | TargetID 3 | p-Value 4 |
---|---|---|---|---|---|---|
PPP1R13L | protein phosphatase 1 regulatory subunit 13-like | −287.4783 | 0.1425181 | 0.5611927 | cg03554552 | 1.78719 × 10−29 |
PPP1CC | protein phosphatase 1 catalytic subunit gamma | −195.8575 | 0.5820595 | 0.9008529 | cg03310453 | 2.59567 × 10−20 |
SCRN2 | secernin 2 | −174.5741 | 0.5376809 | 0.858446 | cg11646887 | 3.48811 × 10−18 |
MYL5 | myosin light chain 5 | −174.3685 | 0.5000765 | 0.831169 | cg18176712 | 3.65721 × 10−18 |
FUCA1 | alpha-L-fucosidase 1 | −166.3722 | 0.6312342 | 0.9132504 | cg24792360 | 2.30558 × 10−17 |
ISYNA1 | inositol-3-phosphate synthase 1 | −161.8102 | 0.4622425 | 0.7933455 | cg09374949 | 6.59144 × 10−17 |
YIPF5 | Yip1 domain family member 5 | −153.572 | 0.4413335 | 0.7704819 | cg04293726 | 4.39339 × 10−16 |
SEMA6C | semaphorin 6C | −149.7812 | 0.4570227 | 0.7800868 | cg25820693 | 1.05167 × 10−15 |
FBN2 | fibrillin 2 | −147.2405 | 0.7476242 | 0.9649287 | cg25084878 | 1.88777 × 10−15 |
RANGNRF | RAN guanine nucleotide release factor | −146.2499 | 0.4167334 | 0.743665 | cg11178443 | 2.37143 × 10−15 |
DCAF16 | DDB1 and CUL4-associated factor 16 | 90.26163 | 0.7206882 | 0.4538092 | cg27127056 | 9.41536 × 10−10 |
SACM1L | SAC1-like phosphatidylinositide phosphatase | 91.75178 | 0.8458125 | 0.6134535 | cg22986271 | 6.6807 × 10−10 |
CACHD1 | cache domain containing 1 | 94.27448 | 0.7917484 | 0.5357191 | cg19304410 | 3.73725 × 10−10 |
UGDH | UDP-glucose 6-dehydrogenase | 97.15292 | 0.8846164 | 0.6643396 | cg25117976 | 1.92623 × 10−10 |
GGTLC2 | gamma-glutamyltransferase light chain 2 | 99.88158 | 0.8204779 | 0.5666317 | cg01457622 | 1.02764 × 10−10 |
C16orf54 | chromosome 16 open reading frame 54 | 101.7236 | 0.2649694 | 0.0511992 | cg23093496 | 6.72419 × 10−11 |
FXN | frataxin | 103.5087 | 0.5243153 | 0.2395225 | cg23667933 | 4.4579 × 10−11 |
RGS11 | regulator of G protein signaling 11 | 104.2319 | 0.4908251 | 0.2102013 | cg01344518 | 3.77407 × 10−11 |
PRICKLE3 | prickle planar cell polarity protein 3 | 105.7841 | 0.3453371 | 0.09902742 | cg10417559 | 2.63992 × 10−11 |
SPATA4 | spermatogenesis associated 4 | 335.9589 | 0.5617582 | 0.2024512 | cg01311285 | 2.53577 × 10−34 |
Gene Symbol | Gene Description | Regulatory Score 1 | Yes-No Ratio 2 |
---|---|---|---|
ECs | |||
JUN | Jun proto-oncogene, AP-1 transcription factor subunit | 2.09 | 1.56 |
CDX2 | caudal type homeobox 2 | 1.77 | 1.62 |
POU2F1 | POU class 2 homeobox 1 | 1.61 | 1.87 |
SREBF2 | sterol regulatory element binding transcription factor 2 | 1.59 | 1.33 |
NKX3-1 | NK3 homeobox 1 | 1.58 | 1.58 |
NHLH1 | nescient helix-loop-helix 1 | 1.39 | 2.6 |
GABPA | GA binding protein transcription factor subunit alpha | 1.38 | 1.24 |
RUNX3 | RUNX family transcription factor 3 | 1.32 | 4.61 |
NRL | neural retina leucine zipper | 1.21 | 1.75 |
MAFK | MAF bZIP transcription factor K | 1.15 | 2.13 |
SMCs | |||
SREBF2 | sterol regulatory element binding transcription factor 2 | 1.8 | 1.5 |
LEF1 | lymphoid enhancer binding factor 1 | 1.78 | 2.26 |
IRF3 | interferon regulatory factor 3 | 1.76 | 2.39 |
WT1 | WT1 transcription factor | 1.74 | 5.13 |
SFPQ | splicing factor proline and glutamine rich | 1.71 | 1.24 |
POU2F1 | POU class 2 homeobox 1 | 1.7 | 3.54 |
RBPJ | recombination signal binding protein for immunoglobulin kappa J region | 1.7 | 1.65 |
DPF2 | double PHD fingers 2 | 1.64 | 1.31 |
PAX5 | paired box 5 | 1.64 | 1.35 |
SREBF1 | sterol regulatory element binding transcription factor 1 | 1.64 | 4.45 |
FBs | |||
RELA | RELA proto-oncogene, NF-kB subunit | 2.27 | 1.9 |
ESR1 | estrogen receptor 1 | 2.09 | 2.44 |
TFAP2A | transcription factor AP-2 alpha | 1.66 | 2.12 |
RUNX3 | RUNX family transcription factor 3 | 1.62 | 1.8 |
ELF3 | E74 like ETS transcription factor 3 | 1.46 | 2.96 |
TFAP2B | transcription factor AP-2 beta | 0 | 2.12 |
TFAP2C | transcription factor AP-2 gamma | 0 | 2.42 |
Master Molecule Name | Gene Symbol | Gene Description | Total Rank 1 |
---|---|---|---|
ECs | |||
PDGFB-isoform1(h) | PDGFB | platelet-derived growth factor subunit B | 9 |
PDGFB-isoform2(h) | PDGFB | platelet-derived growth factor subunit B | 9 |
PDGFB(h) | PDGFB | platelet-derived growth factor subunit B | 11 |
HRS(h) | HGS | hepatocyte growth factor-regulated tyrosine kinase substrate | 13 |
HRS:PtdIns(3)P:SARA:SMAD2 | HGS, SMAD2, ZFYVE9 | SMAD family member 2, hepatocyte growth factor-regulated tyrosine kinase substrate, zinc finger FYVE-type containing 9 | 13 |
HRS:PtdIns(3)P:SARA:SMAD3 | HGS, SMAD3, ZFYVE9 | SMAD family member 3, hepatocyte growth factor-regulated tyrosine kinase substrate, zinc finger FYVE-type containing 9 | 13 |
HRS-isoform1(h) | HGS | hepatocyte growth factor-regulated tyrosine kinase substrate | 13 |
HRS(h){pY} | HGS | hepatocyte growth factor-regulated tyrosine kinase substrate | 13 |
HRS-isoform2(h) | HGS | hepatocyte growth factor-regulated tyrosine kinase substrate | 13 |
HRS(h){pY334} | HGS | hepatocyte growth factor-regulated tyrosine kinase substrate | 13 |
SMCs | |||
HRS(h) | HGS | hepatocyte growth factor-regulated tyrosine kinase substrate | 30 |
HRS:PtdIns(3)P:SARA:SMAD2 | HGS, SMAD2, ZFYVE9 | SMAD family member 2, hepatocyte growth factor-regulated tyrosine kinase substrate, zinc finger FYVE-type containing 9 | 30 |
HRS:PtdIns(3)P:SARA:SMAD3 | HGS, SMAD3, ZFYVE9 | SMAD family member 3, hepatocyte growth factor-regulated tyrosine kinase substrate, zinc finger FYVE-type containing 9 | 30 |
HRS-isoform1(h) | HGS | hepatocyte growth factor-regulated tyrosine kinase substrate | 30 |
HRS(h){pY} | HGS | hepatocyte growth factor-regulated tyrosine kinase substrate | 30 |
HRS-isoform2(h) | HGS | hepatocyte growth factor-regulated tyrosine kinase substrate | 30 |
HRS(h){pY334} | HGS | hepatocyte growth factor-regulated tyrosine kinase substrate | 30 |
Sprouty2(h){p} | SPRY2 | sprouty RTK signaling antagonist 2 | 30 |
Sprouty2(h) | SPRY2 | sprouty RTK signaling antagonist 2 | 31 |
CD23(h) | FCER2 | Fc fragment of IgE receptor II | 32 |
FBs | |||
SOCS-1(h) | SOCS1 | suppressor of cytokine signaling 1 | 21 |
p50:NF-kappaBp65:SOCS-1 | NFKB1, RELA, SOCS1 | RELA proto-oncogene, NF-kB subunit, nuclear factor kappa B subunit 1, suppressor of cytokine signaling 1 | 21 |
p50:NF-kappaBp65{ub}n:SOCS-1 | NFKB1, RELA, SOCS1 | RELA proto-oncogene, NF-kB subunit, nuclear factor kappa B subunit 1, suppressor of cytokine signaling 1 | 21 |
SOCS-1(h) | SOCS1 | suppressor of cytokine signaling 1 | 29 |
IGF-2R(h) | IGF2R | insulin like growth factor 2 receptor | 32 |
G12/13 | GNA12, GNA13, GNB1, GNB1L, GNB2, GNB3, GNB4, GNB5, GNG2, GNG3, GNG5, GNGT1 | G protein subunit alpha 12, G protein subunit alpha 13, G protein subunit beta 1, G protein subunit beta 1 like, G protein subunit beta 2, G protein subunit beta 3, G protein subunit beta 4, G protein subunit beta 5, G protein subunit gamma 2, G protein subunit gamma 3, G protein subunit gamma 5, G protein subunit gamma transducin 1 | 49 |
DHTXisoform1(h) | UVRAG | UV radiation resistance associated | 50 |
F8B(h){gly}n | F8 | coagulation factor VIII | 51 |
F8B(h) | F8 | coagulation factor VIII | 52 |
F8B-isoform2(h) | F8 | coagulation factor VIII | 53 |
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Smetanina, M.A.; Korolenya, V.A.; Kel, A.E.; Sevostyanova, K.S.; Gavrilov, K.A.; Shevela, A.I.; Filipenko, M.L. Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress. Epigenomes 2023, 7, 8. https://doi.org/10.3390/epigenomes7010008
Smetanina MA, Korolenya VA, Kel AE, Sevostyanova KS, Gavrilov KA, Shevela AI, Filipenko ML. Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress. Epigenomes. 2023; 7(1):8. https://doi.org/10.3390/epigenomes7010008
Chicago/Turabian StyleSmetanina, Mariya A., Valeria A. Korolenya, Alexander E. Kel, Ksenia S. Sevostyanova, Konstantin A. Gavrilov, Andrey I. Shevela, and Maxim L. Filipenko. 2023. "Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress" Epigenomes 7, no. 1: 8. https://doi.org/10.3390/epigenomes7010008