The publication is devoted to the consideration of the mechanisms of the adaptive capabilities of the kidney in norm, based on epigenetic control systems of protein biosynthesis. This paper emphasizes the high plasticity of epigenetic mechanisms. The thesis that the epigenetic mechanisms have a high degree of plasticity and perform an important function in adaptive reactions of the kidney, is illustrated by data on the epigenetic transformation of key proteins of various nephron sections. In addition, brief information is given on the possible involvement of epigenetic mechanisms in adaptive rearrangements of arginine vasopressin and natriuretic peptides. High plasticity, accuracy and power of epigenetic systems regulating the adaptive capabilities of the kidney are emphasized.

kidney; adaptation; epigenetics.

Adli M., Parlak M., Li Y., El-Dahr S. Epigenetic States of Nephron Progenitors and Epithelial Differentiation. J Cell Biochem. 2015;116(6): 893–902. doi: 10.1002/jcb.25048

Hilliard S.A, El-Dahr S.S. Epigenetics mechanisms in renal development. Pediatr Nephrol. 2016;31(7):1055–1060. doi: 10.1007/s00467-015-3228-x

Liu H., Chen S., Yao X., Li Y., Chen C.-H., Liu J., Saifudeen Z., El-Dahr S.S. Histone deacetylases 1 and 2 regulate the transcriptional programs of nephron progenitors and renal vesicles.Development. 2018;145,dev153619. doi: 10.1242/dev.153619

Martini A.G., Danser A.H.J. Juxtaglomerular Cell Phenotypic Plasticity. High Blood Press Cardiovasc Prev, 2017;24:231–242. doi: 10.1007/s40292-017-0212-5

Stocher D.P., Klein C.P., Saccomori A.B., August P.M., Martins N.C., Couto P.R.G, Hagen M.E.K., Mattй C. Maternal high-salt diet alters redox state and mitochondrial function in newborn rat offspring’s brain. British Journal of Nutrition, 2018;119: 1003–1011. doi:10.1017/S0007114518000235

Hilliard S.A., El-Dah S.S. Epigenetics of Renal Development and Disease. Yale Journal of Biology and Medicine,2016;89(4):565-573. PMC5168832

Mugatroyd C., Wu Y., Bockmuhl Y., Spengler D. The Janus face of DNA methylation in aging. Aging,2010;2(2):107-110. doi: 10.18632/aging.100124

Greenwood M.P., Greenwood M., Romanova E.V., Mecawi A.S., Paterson A., Sarenac O., Japundzic-Zigon N., Antunes-Rodrigues J., Paton J.F.R., Sweedler J.V., Murphy D. The effects of aging on biosynthetic processes in the rat hypothalamic osmoregulatory neuroendocrine system. Neurobiology of Aging, 2018; 65:178-191. doi.org/10.1016/j.neurobiolaging.2018.01.008

Ho J., Kreidberg J.A. The Long and Short of MicroRNAs in the Kidney. J Am Soc Nephrol,2012;23: 400–404. doi: 10.1681/ASN.2011080797

Trionfini P., Benigni A. MicroRNAs as Master Regulators of Glomerular Function in Health and Disease. J Am Soc Nephrol,2017;28:1686–1696. doi: https://doi.org/10.1681/ASN.2016101117

Tain Y.-L., Huang L.-T., Hsu C.-N. Developmental Programming of Adult Disease: Reprogramming by Melatonin? Int. J. Mol. Sci., 2017; 18: 426. doi: 10.3390/ijms18020426

Lay A.C., Coward R.J.M. The Evolving Importance of Insulin Signaling in Podocyte Health and Disease. Front. Endocrinol,2018;9:693. doi: 10.3389/fendo.2018.00693

Shiels P.G., McGuinness D., Eriksson M., Kooman J.P., Stenvinkel P. The role of epigenetics in renal ageing. Nature Reviews Nephrology, 2017;13:471-482. doi: 10.1038/nrneph.2017.78

Morigi M., Perico L., Benigni A. Sirtuins in Renal Health and Disease. Journal of the American Society of Nephrology, 2018;29(7):1799-1809. doi: 10.1681/ASN.2017111218

Azzi A., Dallmann R., Casserly A., Rehrauer H., Patrignani A., Maier B., Kramer A., Brown S.A. Circadian behavior is light-reprogrammed by plastic DNA methylation, Nature Neuroscience,2014;17:377–382. Doi: 10.1038/nn.3651

Zhang D., Yu Z., Cruz P., Kong Q., Li S., Kone B.C Epigenetics and the control of epithelial sodium channel expression in collecting duct. Kidney International, 2009; 75:260–267. doi:10.1038/ki.2008.475

Wei Q., Bhatt K., He H.-Z., Mi Q.-S., Haase V.H., Dong Z. Targeted Deletion of Dicer from Proximal Tubules Protects against Renal Ischemia-Reperfusion Injury. J Am Soc Nephrol, 2010;21:756–761. doi: 10.1681/ASN.2009070718

Chou Y.-H., Huang T.-M., Chu T.-S. Novel insights into acute kidney injury–chronic kidney disease continuum and the role of renin–angiotensin system. Journal of the Formosan Medical Association,2017;116:652e659. doi: 10.1016/j.jfma.2017.04.026

MacManes M.D. Severe acute dehydration in a desert rodent elicits a transcriptional response that effectively prevents kidney injury. Am J Physiol Renal Physiol, 2017; 313:F262–F272. doi: 10.1152/ajprenal.00067.2017

Taub M. Gene Level Regulation of Na,K-ATPase in the Renal Proximal Tubule Is Controlled by Two Independent but Interacting Regulatory Mechanisms Involving Salt Inducible Kinase 1 and CREB-Regulated Transcriptional Coactivators. Int. J. Mol. Sci, 2018;19:2086. doi: 10.3390/ijms19072086

Gildea J.J., Xu P., Kemp B.A., Carlson J,M., Tran HT, Bigler Wang D, et al. Sodium bicarbonate cotransporter NBCe2 gene variants increase sodium and bicarbonate transport in human renal proximal tubule cells. PLoS ONE, 2018;13(4): e0189464. doi: 10.1371/journal.pone.0189464

Ivy J.R., Evans L.C., Moorhouse R., Richardson RV, Al-Dujaili E.A.S., Flatman P.W., Kenyon C.J., Chapman K.E., Bailey M.A. Renal and Blood Pressure Response to a High-Salt Diet in Mice With Reduced Global Expression of the Glucocorticoid Receptor. Front. Physiol, 2018;9:848. doi: 10.3389/fphys.2018.00848

Takeda Y., Demura M., Wang F., Karashima S., Yoneda T., Kometani M., Hashimoto A., Aono D., Horike S., Meguro-Horike M., Yamagishi M., Takeda Y. Epigenetic Regulation of Aldosterone Synthase Gene by Sodium and Angiotensin II. J Am Heart Assoc, 2018;7:e008281. Doi: 10.1161/JAHA.117.008281

Hua J.X., Ting Z.J., Chan C.H. Ion channels/transporters as epigenetic regulators? A microRNA perspective. Science china Life Sciences,2012;55(9):753–760. doi: 10.1007/s11427-012-4369-9

Mladinov D., Liu Y., Mattson D.L., Liang M. MicroRNAs contribute to the maintenance of cell-type-specific physiological characteristics: miR-192 targets Na+/K+-ATPase b1. Nucleic Acids Research, 2013:41, No. 2 1273–1283. doi: 10.1093/nar/gks1228.

Huang W., Liu H., Wang T., Zhang T., Kuang J., Luo Y., Chung S.S.M., Yuan L., Yang J.Y. Tonicity-responsive microRNAs contribute to the maximal induction of osmoregulatory transcription factor OREBP in response to high-NaCl hypertonicity. Nucleic Acids Research, 2011;39(2):475–485. doi: 10.1093/nar/gkq818

Luo Y., Liu Y., Liu M., Wei J., Zhang Y., Hou J., Huang W., Wang T., Li X., He Y., Ding F., Yuan L., Cai J., Zheng F., Yang J.Y. Sfmbt2 10th intron-hosted miR-466(a/e)-3p are important epigenetic regulators of Nfat5 signaling, osmoregulation and urine concentration in mice. Biochimica et Biophysica Acta, 2014;1839:97–106. doi: 10.1016/j.bbagrm.2013.12.005

Chandrasekaran K., Karolina D.S., Sepramaniam S., Armugam A., Wintour E.M., Bertram J.F., Jeyaseelan K. Role of microRNAs in kidney homeostasis and disease. Kidney International,2012;81:617–627. doi: 10.1038/ki.2011.448

Ichii O., Horino T. MicroRNAs associated with the development of kidney diseases in humans and animals. J Toxicol Pathol,2018;31(1):23–34. doi: 10.1293/tox.2017-0051

Thomas M.J., Fraser D.J., Bowen T.Biogenesis, Stabilization, and Transport of microRNAs in Kidney Health and Disease. Non-coding RNA,2018;4(4):E30. doi: 10.3390/ncrna4040030

Hirohama D., Ayuzawa N., Ueda K., Nishimoto M., Kawarazaki W., Watanabe A., Shimosawa T., Marumo T., Shibata S., Fujita T. Aldosterone Is Essential for Angiotensin II-Induced Upregulation of Pendrin. J Am Soc Nephrol, 2018;29:57–68. doi: 10.1681/ASN.2017030243

Lu C.C., Ma K.L., Ruan X.Z., Liu B.C. Intestinal dysbiosis activates renal renin-angiotensin system contributing to incipient diabetic nephropathy. Int. J. Med. Sci.,2018;15(8):816-822. doi: 10.7150/ijms.25543

Martini A.G., Xa L.K., Lacombe M.-J., Blanchet-Cohen A., Mercure C., Haibe-Kains B., Friesema E.C.H.., van den Meiracker A.H., Gross K.W., Azizi M., Corvol P., Nguyen G., Reudelhuber T.L., Danser A.H.J. Transcriptome Analysis of Human Reninomas as an Approach to Understanding Juxtaglomerular Cell Biology. Hypertension. 2017;69:1145-1155. doi: 10.1161/HYPERTENSIONAHA.117.09179

Sequeira-Lopez M.L.S., Weatherford E.T., Borges G.R., Monteagudo M.C., Pentz E.C., Harfe B.D., Carretero O., Sigmund C.D., Gomez R.A. The MicroRNA-Processing Enzyme Dicer Maintains Juxtaglomerular Cells. J Am Soc Nephrol,2010;21:460–467. doi: 10.1681/ASN.2009090964

Marumo T., Yagi S., Kawarazaki W., Nishimoto M., Ayuzawa N., Watanabe A., Ueda K., Hirahashi J., Hishikawa K., Sakurai H., Shiota K., Fujita T. Diabetes Induces Aberrant DNA Methylation in the Proximal Tubules of the Kidney. J Am Soc Nephrol,2015;26:2388–2397. doi: 10.1681/ASN.2014070665

Martini A.G., Danser A.H.J. Juxtaglomerular Cell Phenotypic Plasticity. High Blood Press Cardiovasc Prev,2017;24:231–242. doi: 10.1007/s40292-017-0212-5

Hohl M., Wagner M., Reil J.-C., Mьller S.-A., Tauchnitz M., Zimmer A.M., Lehmann L.H., Thiel G., Bцhm M., Backs J., Maack C. HDAC4 controls histone methylation in response to elevated cardiac load. J Clin Invest.2013;123(3):1359–1370. doi: 10.1172/JCI61084

Sergeeva I.A., Hooijkaas I.B., Ruijter J.M., van der Made I., de Groot N.E., van de Werken H.J.G., Creemers E.E., Christoffels V.M. Identification of a regulatory domain controlling the Nppa-Nppb gene cluster during heart development and stress. Development,2016;143:2135-2146. doi: 10.1242/dev.132019

Li Y., Cai X., Guan Y., Wang L., Wang S., Li Y. et al. Adiponectin Upregulates MiR-133a in Cardiac Hypertrophy through AMPK Activation and Reduced ERK1/2 Phosphorylation. PLoS ONE,2016;11(2):e0148482. doi: 10.1371/journal.pone.0148482

Hayashi M., Arima H., Goto M., Banno R., Watanabe M., Sato I., Nagasaki H., Oiso Y. Vasopressin gene transcription increases in response to decreases in plasma volume, but not to increases in plasma osmolality, in chronically dehydrated rats. Am J Physiol Endocrinol Metab,2006;290:E213–E217. doi: 10.1152/ajpendo.00158.2005

Greenwood M.P., Greenwood M., Gillard B.T., Loh S.Y., Paton J.F.R., Murphy D. Epigenetic Control of the Vasopressin Promoter Explains Physiological Ability to Regulate Vasopressin Transcription in Dehydration and Salt Loading States in the Rat. Journal of Neuroendocrinology, 2016;28(4):10.1111/jne.12371. doi: 10.1111/jne.12371

Augera C.J., Cossa D., Augera A.P., Forbes-Lorman R.M. Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain. PNAS,2011;108(10):4242–4247. doi: 10.1073/pnas.1100314108

Park E.-J., Kwon T.H. A Minireview on Vasopressin-regulated Aquaporin-2 in Kidney Collecting Duct Cells. Electrolyte Blood Press,2015;13:1-6. doi: 10.5049/EBP.2015.13.1.1

Jung H.J., Kwon T.-H. Molecular mechanisms regulating aquaporin-2 in kidney collecting duct. Am J Physiol Renal Physiol,2016,311:F1318–F1328. doi: 10.1152/ajprenal.00485.2016

Bourque C.W. Central mechanisms of osmosensation and systemic osmoregulation. Nat Rev Neurosci. 2008;9(7):519-531. doi: 10.1038/nrn2400

Thornton S.N. Thirst and hydration: physiology and consequences of dysfunction. Physiol Behav. 2010;100(1):15-21. doi: 10.1016/j.physbeh.2010.02.026

Greenwood M.P., Mecawi A.S.,Hoe S.Z., Mustafa M.R., Johnson K.R., Al-Mahmoud G.A., Elias L.L.K., Paton J.F.R., Antunes-Rodrigues J., Gainer H., Murphy D., Hindmarch C.C.T. A comparison of physiological and transcriptome responses to water deprivation and salt loading in the rat supraoptic nucleus. Am J Physiol Regul Integr Comp Physiol. 2015; 308: R559–R568. doi: 10.1152/ajpregu.00444.2014

Park E.-J., Kwon T.-H. A Minireview on Vasopressin-regulated Aquaporin-2 in Kidney Collecting Duct Cells. Electrolyte Blood Press. 2015; 13(1): 1–6. doi: 10.5049/EBP.2015.13.1.1

Zhuo J.L., Li X.C. New Insights and Perspectives on Intrarenal Renin-Angiotensin System: Focus on Intracrine/Intracellular Angiotensin II. Peptides. 2011; 32(7): 1551–1565. doi: 10.1016/j.peptides.2011.05.012

Kurtz A. Control of renin synthesis and secretion. Am J Hypertens. 2012;25(8):839-847. doi: 10.1038/ajh.2011.246

Gomez R.A., Sequeira-Lopez M.L.S. Renin cells in homeostasis, regeneration and immune defence mechanisms. Nat Rev Nephrol. 2018;14(4):231-245. doi: 10.1038/nrneph.2017.186

Kuwahara К., Nakao К. Regulation and signifcance of atrial and brain natriuretic peptides as cardiac hormones. Endocrine Journal 2010;57(7):555-565. PMID: 20571250

Nakagawa Y., Nishikimi T., Kuwahara K.Atrial and brain natriuretic peptides: Hormones secreted from the heart. Peptides. 2019;111:18-25. doi: 10.1016/j.peptides.2018.05.012

Kondo N., Arima H., Banno R., Kuwahara S., Sato I., Oiso Y. Osmoregulation of vasopressin release and gene transcription under acute and chronic hypovolemia in rats. Am J Physiol Endocrinol Metab. 2004; 286(3): E337–E346. PMID:14613925. doi: 10.1152/ajpendo.00328.2003

Hindmarch C.C.T., Murphy D. The Transcriptome and the Hypothalamo Neurohypophyseal System. Pediatric Neuroendocrinology. Endocr Dev. 2010;17:1–10. doi: 10.1159/000262523

Hindmarch C., Yao S., Beighton G., Paton J., Murphy D. A comprehensive description of the transcriptome of the hypothalamoneurohypophyseal system in euhydrated and dehydrated rats. PNAS, 2006;103(5): 1609–1614. PMID:16432224. PMCID:PMC1360533. doi: 10.1073/pnas.0507450103

Mitchell N.C., Gilman T.L., Daws L.C., Toney G.M. High Salt Intake Enhances Swim Stress-Induced PVN Vasopressin Cell Activation and Active Stress Coping Psychoneuroendocrinology. 2018;93:29-38. doi: 10.1016/j.psyneuen.2018.04.003

Yue C., Mutsuga N., Sugimura Y., Verbalis J., Gainer H. Differential Kinetics of Oxytocin and Vasopressin Heteronuclear RNA Expression in the Rat Supraoptic Nucleus in Response to Chronic Salt Loading In vivo. Journal of Neuroendocrinology. 2008;20:227–232. PMID:18088359. doi: 10.1111/j.1365-2826.2007.01640.x

Hindmarch C.C., Murphy D. The transcriptome and the hypothalamo-neurohypophyseal system. Endocr Dev. 2010;17:1-10. doi: 10.1159/000262523

Qiu J., Yao S., Hindmarch C., Antunes V., Paton J., Murphy D. Transcription Factor Expression in the HypothalamoNeurohypophyseal System of the Dehydrated Rat: Upregulation of Gonadotrophin Inducible Transcription Factor 1 mRNA Is Mediated by cAMP-Dependent Protein Kinase A. J. Neurosci.2007;27(9):2196–2203. doi: 10.1523/JNEUROSCI.5420-06.2007

Johnson K.R., Hindmarch C.C.T., Salinas Y.D., Shi Y., Greenwood M., Hoe S.Z., et al. (2015) A RNASeq Analysis of the Rat Supraoptic Nucleus Transcriptome: Effects of Salt Loading on Gene Expression. PLoS ONE. 2015;10(4): e0124523. doi: 10.1371/journal.pone.0124523

Ponzio T.A., Fields R.L., Rashid O.M., Salinas Y.D., Lubelski D., Gainer H. Cell-Type Specific Expression of the Vasopressin Gene Analyzed by AAV Mediated Gene Delivery of Promoter Deletion Constructs into the Rat SON In Vivo. PloS One. 2012;7(11):e48860. doi: 10.1371/journal.pone.0048860

Kawasaki M., Ponzio T.A., Yue C., Fields R.L., Gainer H. Neurotransmitter regulation of c-fos and vasopressin gene expression in the rat supraoptic nucleus. Exp Neurol. 2009; 219(1): 212–222. doi: 10.1016/j.expneurol.2009.05.019

Stewart L., Hindmarch C.C.T., Qiu J., Tung Y.-C. L., Yeo G.S.H., Murphy D. Hypothalamic Transcriptome Plasticity in Two Rodent Species Reveals Divergent Differential Gene Expression But Conserved Pathways. Journal of Neuroendocrinology. 2011; 23:177–185. PMID:21070396. doi: 10.1111/j.1365-2826.2010.02093.x

Archer T. Epigenetic Changes Induced by Exercise. Journal of Reward Defciency Syndrome. 2015;1(2):71-74

Loh S.-Y., Jahans-Price T., Greenwood M.P., Greenwood M., Hoe S.-Z., Konopacka A., Campbell C., Murphy D., Hindmarch C.C.T. Unsupervised Network Analysis of the Plastic Supraoptic Nucleus Transcriptome Predicts Caprin2 Regulatory Interactions. eNeuro.2017;4(6). pii: ENEURO.0243-17.2017. doi: 10.1523/ENEURO.0243-17.2017

Konopacka A., Greenwood M., Loh S.-Y., Paton J., Murphy D. RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response. eLife 2015;4:e09656. doi: 10.7554/eLife.09656. PMID:26559902.

Konopacka A., Qiu J., Yao S.T., Greenwood M.P., Greenwood M., Lancaster T., Inoue W., Mecawi A.S., Vechiato F.M., de Lima J.B., Coletti R., Hoe S.Z., Martin A., Lee J., Joseph M., Hindmarch C., Paton J., Antunes-Rodrigues J., Bains J., Murphy D. Osmoregulation requires brain expression of the renal Na-K-2Cl cotransporter NKCC2. J Neurosci.2015;35(13):5144-5155. doi: 10.1523/JNEUROSCI.4121-14.2015

Knepper M.A., Kwon T.-H., Nielsen S. Molecular Physiology of Water Balance. N Engl J Med. 2015; 372(14): 1349–1358. doi: 10.1056/NEJMra1404726.

Qian Q. Salt, water and nephron: Mechanisms of action and link to hypertension and chronic kidney disease. Nephrology (Carlton). 2018; 23(Suppl Suppl 4): 44–49. doi: 10.1111/nep.13465. PMID: 30298656.

Sanghi A., Zaringhalam M., Corcoran C.C., Saeed F., Hoffert J.D., Sandoval P., Pisitkun T., Knepper M.A. A knowledge base of vasopressin actions in the kidney. Am J Physiol Renal Physiol. 2014;307: F747–F755. doi: 10.1152/ajprenal.00012.2014.

Roos K.P., Bugaj V., Mironova E., Stockand J.D., Ramkumar N., Rees S., Kohan D.E.Adenylyl Cyclase VI Mediates Vasopressin-Stimulated ENaC Activity. J Am Soc Nephrol. 2013; 24(2): 218–227. doi:10.1681/ASN.2012050449. PMCID: PMC3559481. PMID: 23264685.

Wilson J.L.L., Miranda C.A., Knepper M.A. Vasopressin and the Regulation of Aquaporin-2. Clin Exp Nephrol. 2013; 17(6): 10.1007/s10157-013-0789-5. doi:10.1007/s10157-013-0789-5. PMID: 23584881.

Yua M.-J., Miller R.L., Uawithya P., Rinschen M.M., Khositseth S., Braucht D.W.W., Chou C.L., Pisitkun T., Nelson R.D., Knepper M.A. Systems-level analysis of cell-specific AQP2 gene expression in renal collecting duct. PNAS. 2009;106(7): 2441–2446. doi: 10.1073/pnas.0813002106

Jung H.J., Kwon T.H. Molecular mechanisms regulating aquaporin-2 in kidney collecting duct. Am J Physiol Renal Physiol. 2016; 311: F1318 –F1328. doi: 10.1152/ajprenal.00485.2016

Xiao Z., Chen L., Zhou Q., Zhang W. Dot1l deficiency leads to increased intercalated cells and upregulation of V-ATPase B1 in mice. Exp Cell Res. 2016; 344(2): 167–175. doi: 10.1016/j.yexcr.2015.09.014

Bodden C., van den Hove D., Lesch K.-P., Sachser N. Impact of varying social experiences during life history on behaviour, gene expression, and vasopressin receptor gene methylation in mice. Sci Rep. 2017; 7: 8719. doi: 10.1038/s41598-017-09292-0. PMID: 28821809

Frieling H., Bleich S., Otten J., Ro¨mer K.D., Kornhuber J., de Zwaan M., Jacoby G.E., Wilhelm J., Hillemacher T. Epigenetic Downregulation of Atrial Natriuretic Peptide but not Vasopressin mRNA Expression in Females with Eating Disorders is Related to Impulsivity. Neuropsychopharmacology. 2008;33:2605–2609. doi: 10.1038/sj.npp.1301662

Gardner D.G., Chen S., Glenn D.J., Grigsby C.L. Molecular Biology of the Natriuretic Peptide System Implications for Physiology and Hypertension. Hypertension. 2007;49:419-426. doi: 10.1161/01.HYP.0000258532.07418.fa

Ichiki T., Burnett J.C. Atrial Natriuretic Peptide. Old But New Therapeutic in Cardiovascular Diseases. Circ J. 2017; 81: 913–919. doi: 10.1253/circj.CJ-17-0499

Nakagawa Y., Nishikimi T., Kuwahara K. Atrial and brain natriuretic peptides: Hormones secreted from the heart. Peptides. 2019;111:18-25. doi: 10.1016/j.peptides.2018.05.012. PMID:29859763

Sergeeva I.A., Christoffels V.M. Regulation of expression of atrial and brain natriuretic peptide, biomarkers for heart developmentand disease. Biochim Biophys Acta. 2013;1832(12):2403-2413. doi: 10.1016/j.bbadis.2013.07.003

Dong L., Wang H., Dong N., Zhang Ce., Xue B., Wu Q. Localization of corin and atrial natriuretic peptide expression in human renal segments. Clin Sci (Lond). 2016; 130(18): 1655–1664. doi: 10.1042/CS20160398

Pandey K.N. Molecular and genetic aspects of guanylyl cyclase natriuretic peptide receptor-A in regulation of blood pressure and renal function. Physiol Genomics. 2018;50(11):913-928. doi: 10.1152/physiolgenomics.00083.2018

DiSalvo T.G. Epigenetic regulation in heart failure: part II DNA and chromatin. Cardiol Rev. 2015;23(6):269-281. doi: 10.1097/CRD.0000000000000074

Man J., Barnett P., Christofels V.M. Structure and function of the Nppa–Nppb cluster locus during heart development and disease. Cell Mol Life Sci. 2018;75(8):1435-1444. doi: 10.1007/s00018-017-2737-0

Pandey K.N. Guanylyl Cyclase/Atrial Natriuretic Peptide Receptor-A: Role in the Pathophysiology of Cardiovascular Regulation. Can J Physiol Pharmacol. 2011; 89(8): 557–573. doi: 10.1139/y11-054

Kumar P., Periyasamy R., Das S., Neerukonda S., Mani I., Pandey K.N. All-Trans Retinoic Acid and Sodium Butyrate Enhance Natriuretic Peptide Receptor A Gene Transcription: Role of Histone Modification. Mol Pharmacol. 2014; 85(6):946-957. doi: 10.1124/mol.114.092221

Huang L., Xi Z., Wang C, Zhang Y., Yang Z., Zhang S., Chen Y., Zuo Z. Phenanthrene exposure induces cardiac hypertrophy via reducing miR-133a expression by DNAmethylation. Sci Rep. 2016;6:20105. doi: 10.1038/srep20105

Ito E., Miyagawa S., Fukushima S., Yoshikawa Y., Saito S., Saito T., Harada A., Takeda M., Kashiyama N., Nakamura Y., Shiozaki M., Toda K., Sawa Y. Histone Modification Is Correlated With Reverse Left Ventricular Remodeling in Nonischemic Dilated Cardiomyopathy. Ann Thorac Surg 2017;104:1531–1539. doi: 10.1016/j.athoracsur.2017.04.046

Shen K., Tu T., Yuan Z., Yi J., Zhou Y., Liao X., Liu Q., Zhou X. DNA methylation dysregulations in valvular atrial fibrillation. Clinical Cardiology. 2017;40:686–691. doi: 10.1002/clc.22715

Hohl M., Wagner M., Reil J.-C., Müller S.A., Tauchnitz M., Zimmer A.M., Lehmann L.H., Thiel G., Böhm M., Backs J., Maack C. HDAC4 controls histone methylation in response to elevated cardiac load. J Clin Invest. 2013;123(3):1359–137. doi: 10.1172/JCI61084

Sergeeva I.A., Hooijkaas I.B., Ruijter J. M., van der Made I., de Groot N.E., van de Werken H.J.G., Creemers E.E. Christoffels V.M. Identification of a regulatory domain controlling the Nppa-Nppb gene cluster during heart development and stress. Development. 2016; 143(12):2135-2146. doi: 10.1242/dev.132019

Kumar P., Pandey K.N. Cooperative activation of npr1 gene transcription and expression by interaction of ets-1 and P300. Hypertension. 2009; 54(1): 172–178. doi:10.1161/HYPERTENSIONAHA.109.133033. PMID: 19487584.

Kumar P., Tripathi S., Pandey K.N. Histone Deacetylase Inhibitors Modulate the Transcriptional Regulation of Guanylyl Cyclase/Natriuretic Peptide Receptor-A Gene. Interactive roles of modified histones, histone acetyltransferase, p300, and Sp1. Journal of biological chemistry. 2014; 289(10):6991-7002. doi: 10.1074/jbc.M113.511444

Chen L., Yang T., Lu D.W., Zhao H., Feng Y.L., Chen H., Chen D.Q., Vaziri N.D., Zhao Y.Y. Central role of dysregulation of TGF-β/Smad in CKD progression and potential targets of its treatment. Biomed Pharmacother. 2018;101:670-681. doi: 10.1016/j.biopha.2018.02.090

Sen A., Kumar P., Garg R., Lindsey S.H., Katakam P.V.G., Bloodworth M., Pandey K.N. Transforming growth factor b1 antagonizes the transcription, expression and vascular signaling of guanylyl cyclase/natriuretic peptide receptor A – role of dEF1. FEBS Journal. 2016; 283(9):1767–1781. doi: 10.1111/febs.13701. PMID:26934489.