دورية أكاديمية
أعرض في EDS

Inhibition of Renin Expression Is Regulated by an Epigenetic Switch From an Active to a Poised State.

التفاصيل البيبلوغرافية
العنوان: Inhibition of Renin Expression Is Regulated by an Epigenetic Switch From an Active to a Poised State.
المؤلفون: Smith JP; Department of Pediatrics, Child Health Research Center (J.P.S., R.P., S.M., M.L.S.S.-L., R.A.G.), University of Virginia, Charlottesville, VA., Paxton R; Department of Pediatrics, Child Health Research Center (J.P.S., R.P., S.M., M.L.S.S.-L., R.A.G.), University of Virginia, Charlottesville, VA.; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria (R.P.)., Medrano S; Department of Pediatrics, Child Health Research Center (J.P.S., R.P., S.M., M.L.S.S.-L., R.A.G.), University of Virginia, Charlottesville, VA., Sheffield NC; Center for Public Health Genomics (N.C.S.), University of Virginia, Charlottesville, VA.; Department of Public Health Sciences (N.C.S.), University of Virginia, Charlottesville, VA.; Department of Biomedical Engineering (N.C.S.), University of Virginia, Charlottesville, VA.; Department of Biochemistry and Molecular Genetics (N.C.S.), University of Virginia, Charlottesville, VA., Sequeira-Lopez MLS; Department of Pediatrics, Child Health Research Center (J.P.S., R.P., S.M., M.L.S.S.-L., R.A.G.), University of Virginia, Charlottesville, VA., Gomez RA; Department of Pediatrics, Child Health Research Center (J.P.S., R.P., S.M., M.L.S.S.-L., R.A.G.), University of Virginia, Charlottesville, VA.
المصدر: Hypertension (Dallas, Tex. : 1979) [Hypertension] 2024 Sep; Vol. 81 (9), pp. 1869-1882. Date of Electronic Publication: 2024 Jul 11.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Lippincott, Williams & Wilkins Country of Publication: United States NLM ID: 7906255 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4563 (Electronic) Linking ISSN: 0194911X NLM ISO Abbreviation: Hypertension Subsets: MEDLINE
أسماء مطبوعة: Publication: : Hagerstown, MD : Lippincott, Williams & Wilkins
Original Publication: [Dallas, Tex.] : [American Heart Association], [©1979]-
مواضيع طبية MeSH: Epigenesis, Genetic* , Renin*/metabolism , Renin*/genetics , Transcription Factors*/genetics , Transcription Factors*/metabolism, Animals ; Mice ; Gene Expression Regulation ; Juxtaglomerular Apparatus/metabolism ; p300-CBP Transcription Factors/metabolism ; p300-CBP Transcription Factors/genetics ; Bromodomain Containing Proteins ; Nuclear Proteins
مستخلص: Background: Renin-expressing cells are myoendocrine cells crucial for the maintenance of homeostasis. Renin is regulated by cAMP, p300 (histone acetyltransferase p300)/CBP (CREB-binding protein), and Brd4 (bromodomain-containing protein 4) proteins and associated pathways. However, the specific regulatory changes that occur following inhibition of these pathways are not clear.
Methods: We treated As4.1 cells (tumoral cells derived from mouse juxtaglomerular cells that constitutively express renin) with 3 inhibitors that target different factors required for renin transcription: H-89-dihydrochloride, PKA (protein kinase A) inhibitor; JQ1, Brd4 bromodomain inhibitor; and A-485, p300/CBP inhibitor. We performed assay for transposase-accessible chromatin with sequencing (ATAC-seq), single-cell RNA sequencing, cleavage under targets and tagmentation (CUT&Tag), and chromatin immunoprecipitation sequencing for H3K27ac (acetylation of lysine 27 of the histone H3 protein) and p300 binding on biological replicates of treated and control As4.1 cells.
Results: In response to each inhibitor, Ren1 expression was significantly reduced and reversible upon washout. Chromatin accessibility at the Ren1 locus did not markedly change but was globally reduced at distal elements. Inhibition of PKA led to significant reductions in H3K27ac and p300 binding specifically within the Ren1 super-enhancer region. Further, we identified enriched TF (transcription factor) motifs shared across each inhibitory treatment. Finally, we identified a set of 9 genes with putative roles across each of the 3 renin regulatory pathways and observed that each displayed differentially accessible chromatin, gene expression, H3K27ac, and p300 binding at their respective loci.
Conclusions: Inhibition of renin expression in cells that constitutively synthesize and release renin is regulated by an epigenetic switch from an active to poised state associated with decreased cell-cell communication and an epithelial-mesenchymal transition. This work highlights and helps define the factors necessary for renin cells to alternate between myoendocrine and contractile phenotypes.
Competing Interests: None.
References: Biochim Biophys Acta Mol Cell Res. 2017 Feb;1864(2):367-381. (PMID: 27888097)
Mol Cell Biol. 1998 Dec;18(12):7038-51. (PMID: 9819391)
J Am Soc Nephrol. 2015 Jan;26(1):67-80. (PMID: 24904090)
Nucleic Acids Res. 2023 Jul 21;51(13):6784-6805. (PMID: 37264934)
J Clin Invest. 2018 Nov 1;128(11):4787-4803. (PMID: 30130256)
FEBS Lett. 2011 Jun 6;585(11):1663-72. (PMID: 21570968)
Am J Physiol Endocrinol Metab. 2019 Jun 1;316(6):E1050-E1060. (PMID: 30835506)
Cancer Lett. 2016 May 28;375(1):9-19. (PMID: 26902421)
BMC Mol Cell Biol. 2020 Jul 20;21(1):55. (PMID: 32690000)
Nature. 2018 Aug;560(7719):494-498. (PMID: 30089906)
Methods Mol Biol. 2013;1067:105-24. (PMID: 23975789)
Innovation (Camb). 2021 Jul 01;2(3):100141. (PMID: 34557778)
Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21931-6. (PMID: 21106759)
Bioinformatics. 2011 Apr 1;27(7):1017-8. (PMID: 21330290)
Nature. 2012 Jan 04;481(7381):389-93. (PMID: 22217937)
J Pineal Res. 2016 Apr;60(3):313-26. (PMID: 26797926)
FASEB J. 2015 Sep;29(9):3773-87. (PMID: 26023182)
Mol Cell. 2017 Feb 16;65(4):631-643.e4. (PMID: 28212749)
Circ Res. 2021 Apr 2;128(7):887-907. (PMID: 33793334)
Nat Rev Mol Cell Biol. 2015 Mar;16(3):144-54. (PMID: 25650801)
PLoS Comput Biol. 2022 Aug 30;18(8):e1010378. (PMID: 36040971)
Nat Rev Mol Cell Biol. 2001 Nov;2(11):827-37. (PMID: 11715049)
Nephron Physiol. 2010;116(1):p1-8. (PMID: 20530971)
OMICS. 2012 May;16(5):284-7. (PMID: 22455463)
Cell Rep. 2023 Mar 28;42(3):112210. (PMID: 36881507)
Physiol Rev. 2010 Apr;90(2):607-73. (PMID: 20393195)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Nat Rev Nephrol. 2011 Oct 18;7(12):684-96. (PMID: 22009250)
Transplantation. 2016 Feb;100(2):325-333. (PMID: 26502369)
J Biol Chem. 1990 Nov 15;265(32):19916-22. (PMID: 2174057)
Nucleic Acids Res. 2015 Jan;43(Database issue):D117-22. (PMID: 25378322)
PLoS One. 2012;7(9):e44615. (PMID: 22970268)
Nucleic Acids Res. 2022 Jan 7;50(D1):D687-D692. (PMID: 34788843)
Front Oncol. 2022 Jun 21;12:925687. (PMID: 35800049)
Nat Biotechnol. 2020 Mar;38(3):276-278. (PMID: 32055031)
Genome Biol. 2019 Dec 23;20(1):296. (PMID: 31870423)
Nucleic Acids Res. 2015 Jul 1;43(W1):W39-49. (PMID: 25953851)
Eur J Pharm Sci. 2023 Oct 1;189:106531. (PMID: 37479045)
J Cell Physiol. 2019 May;234(5):5379-5389. (PMID: 30350856)
PPAR Res. 2013;2013:451016. (PMID: 24288524)
J Biol Chem. 2006 Oct 20;281(42):31753-61. (PMID: 16895910)
Cell. 2018 Jul 26;174(3):716-729.e27. (PMID: 29961576)
FEBS Open Bio. 2022 Jul;12(7):1353-1364. (PMID: 35451213)
Cell. 2014 Sep 11;158(6):1431-1443. (PMID: 25215497)
High Blood Press Cardiovasc Prev. 2017 Sep;24(3):231-242. (PMID: 28527017)
Cell Mol Life Sci. 2013 Nov;70(21):3989-4008. (PMID: 23307074)
PLoS Biol. 2008 Jul 22;6(7):e184. (PMID: 18651794)
Development. 2003 Jul;130(14):3175-85. (PMID: 12783789)
Nucleic Acids Res. 1992 Jul 25;20(14):3617-23. (PMID: 1641328)
F1000Res. 2016 Jun 20;5:1438. (PMID: 27508061)
Kidney Int. 2010 Jan;77(2):110-7. (PMID: 19907416)
Oncotarget. 2017 Oct 6;8(60):101720-101734. (PMID: 29254199)
Cell Syst. 2015 Dec 23;1(6):417-425. (PMID: 26771021)
J Am Soc Nephrol. 2011 Dec;22(12):2213-25. (PMID: 22034642)
Int J Oncol. 2006 Feb;28(2):487-96. (PMID: 16391805)
Nat Methods. 2013 Dec;10(12):1213-8. (PMID: 24097267)
Nat Commun. 2022 Jan 24;13(1):457. (PMID: 35075189)
Genome Biol. 2008;9(9):R137. (PMID: 18798982)
Oncogene. 2008 Nov 24;27(55):6981-93. (PMID: 19029939)
J Neurosci. 1999 Jun 1;19(11):4337-48. (PMID: 10341237)
Nucleic Acids Res. 2018 Jan 25;46(2):e9. (PMID: 29126307)
Mol Cell. 2010 May 28;38(4):576-89. (PMID: 20513432)
Cancers (Basel). 2019 Jul 23;11(7):. (PMID: 31340499)
J Am Soc Nephrol. 2015 Jan;26(1):107-20. (PMID: 25012166)
Nat Biotechnol. 2024 Feb;42(2):293-304. (PMID: 37231261)
Bioinformatics. 2017 Apr 15;33(8):1179-1186. (PMID: 28088763)
Immunity. 2010 Mar 26;32(3):317-28. (PMID: 20206554)
J Cell Biol. 2012 Jun 25;197(7):983-96. (PMID: 22734003)
Biochim Biophys Acta. 2003 Feb 20;1625(3):280-90. (PMID: 12591615)
Bioinformatics. 2013 Jan 1;29(1):15-21. (PMID: 23104886)
Cell Stem Cell. 2017 Mar 2;20(3):303-314.e5. (PMID: 28041894)
J Am Soc Nephrol. 2006 Jan;17(1):17-25. (PMID: 16291837)
Chem Rev. 2015 Mar 25;115(6):2419-52. (PMID: 25594381)
Am J Physiol Gastrointest Liver Physiol. 2002 Jun;282(6):G1035-44. (PMID: 12016129)
NAR Genom Bioinform. 2021 Nov 23;3(4):lqab101. (PMID: 34859208)
Nat Biotechnol. 2010 May;28(5):495-501. (PMID: 20436461)
BMC Bioinformatics. 2010 May 11;11:237. (PMID: 20459804)
Cell. 2019 Jun 13;177(7):1888-1902.e21. (PMID: 31178118)
J Cell Sci. 2005 Aug 1;118(Pt 15):3371-85. (PMID: 16079281)
Pharmaceuticals (Basel). 2023 Jan 11;16(1):. (PMID: 36678607)
Nat Commun. 2019 Apr 29;10(1):1930. (PMID: 31036827)
Circ Res. 2021 Jul 9;129(2):262-276. (PMID: 33993729)
Am J Physiol. 1997 Nov;273(5):F731-8. (PMID: 9374836)
Circ Res. 2019 Apr 26;124(9):1309-1322. (PMID: 30801233)
Cancer Res. 2019 Oct 1;79(19):5102-5112. (PMID: 31337651)
J Biol Chem. 1997 Jan 24;272(4):2412-20. (PMID: 8999953)
Cell Mol Life Sci. 2010 Jul;67(13):2271-81. (PMID: 20237821)
Mol Cancer. 2021 Oct 27;20(1):140. (PMID: 34706732)
Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1849-E1858. (PMID: 29432158)
Cancer Res. 2009 Apr 15;69(8):3272-7. (PMID: 19351819)
Nat Commun. 2017 Jan 16;8:14049. (PMID: 28091601)
EBioMedicine. 2018 May;31:217-225. (PMID: 29759484)
Genome Biol. 2007;8(2):R24. (PMID: 17324271)
Int J Mol Sci. 2020 Nov 06;21(21):. (PMID: 33172216)
Aging Cell. 2023 Jul;22(7):e13858. (PMID: 37154113)
Nucleic Acids Res. 2022 Jan 7;50(D1):D165-D173. (PMID: 34850907)
PLoS Genet. 2019 Jun 27;15(6):e1008216. (PMID: 31246957)
FASEB J. 2019 Apr;33(4):5704-5715. (PMID: 30673513)
Oncogene. 2000 Dec 18;19(55):6432-42. (PMID: 11175359)
معلومات مُعتمدة: P50 DK096373 United States DK NIDDK NIH HHS; R01 DK116196 United States DK NIDDK NIH HHS; R01 DK116718 United States DK NIDDK NIH HHS; R01 HL148044 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: chromatin; data analysis; multiomics; nuclear proteins; renin
المشرفين على المادة: EC 3.4.23.15 (Renin)
0 (Transcription Factors)
EC 2.3.1.48 (p300-CBP Transcription Factors)
0 (Brd4 protein, mouse)
0 (Bromodomain Containing Proteins)
0 (Nuclear Proteins)
تواريخ الأحداث: Date Created: 20240711 Date Completed: 20240814 Latest Revision: 20240823
رمز التحديث: 20240823
مُعرف محوري في PubMed: PMC11337216
DOI: 10.1161/HYPERTENSIONAHA.124.22886
PMID: 38989586
قاعدة البيانات: MEDLINE
الوصف
تدمد:1524-4563
DOI:10.1161/HYPERTENSIONAHA.124.22886