دورية أكاديمية
أعرض في EDS

Differential usage of DNA modifications in neurons, astrocytes, and microglia.

التفاصيل البيبلوغرافية
العنوان: Differential usage of DNA modifications in neurons, astrocytes, and microglia.
المؤلفون: Tooley KB; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.; Genes & Human Disease Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK, 73104, USA., Chucair-Elliott AJ; Genes & Human Disease Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK, 73104, USA., Ocañas SR; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.; Genes & Human Disease Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK, 73104, USA., Machalinski AH; Genes & Human Disease Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK, 73104, USA., Pham KD; Genes & Human Disease Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK, 73104, USA., Hoolehan W; Genes & Human Disease Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK, 73104, USA., Kulpa AM; Genes & Human Disease Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK, 73104, USA., Stanford DR; Center for Biomedical Data Sciences, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA., Freeman WM; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. bill-freeman@omrf.org.; Department of Biochemistry, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. bill-freeman@omrf.org.; Oklahoma City Veterans Affairs Medical Center, Oklahoma City, OK, USA. bill-freeman@omrf.org.
المصدر: Epigenetics & chromatin [Epigenetics Chromatin] 2023 Nov 13; Vol. 16 (1), pp. 45. Date of Electronic Publication: 2023 Nov 13.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101471619 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-8935 (Electronic) Linking ISSN: 17568935 NLM ISO Abbreviation: Epigenetics Chromatin Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central
مواضيع طبية MeSH: Microglia* , Astrocytes*, Mice ; Animals ; DNA Methylation ; DNA ; Neurons
مستخلص: Background: Cellular identity is determined partly by cell type-specific epigenomic profiles that regulate gene expression. In neuroscience, there is a pressing need to isolate and characterize the epigenomes of specific CNS cell types in health and disease. In this study, we developed an in vivo tagging mouse model (Camk2a-NuTRAP) for paired isolation of neuronal DNA and RNA without cell sorting and then used this model to assess epigenomic regulation, DNA modifications in particular, of gene expression between neurons and glia.
Results: After validating the cell-specificity of the Camk2a-NuTRAP model, we performed TRAP-RNA-Seq and INTACT-whole genome oxidative bisulfite sequencing (WGoxBS) to assess the neuronal translatome and epigenome in the hippocampus of young mice (4 months old). WGoxBS findings were validated with enzymatic methyl-Seq (EM-Seq) and nanopore sequencing. Comparing neuronal data to microglial and astrocytic data from NuTRAP models, microglia had the highest global mCG levels followed by astrocytes and then neurons, with the opposite pattern observed for hmCG and mCH. Differentially modified regions between cell types were predominantly found within gene bodies and distal intergenic regions, rather than proximal promoters. Across cell types there was a negative correlation between DNA modifications (mCG, mCH, hmCG) and gene expression at proximal promoters. In contrast, a negative correlation of gene body mCG and a positive relationship between distal promoter and gene body hmCG with gene expression was observed. Furthermore, we identified a neuron-specific inverse relationship between mCH and gene expression across promoter and gene body regions.
Conclusions: Neurons, astrocytes, and microglia demonstrate different genome-wide levels of mCG, hmCG, and mCH that are reproducible across analytical methods. However, modification-gene expression relationships are conserved across cell types. Enrichment of differential modifications across cell types in gene bodies and distal regulatory elements, but not proximal promoters, highlights epigenomic patterning in these regions as potentially greater determinants of cell identity. These findings also demonstrate the importance of differentiating between mC and hmC in neuroepigenomic analyses, as up to 30% of what is conventionally interpreted as mCG can be hmCG, which often has a different relationship to gene expression than mCG.
(© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
التعليقات: Update of: bioRxiv. 2023 Jun 07:2023.06.05.543497. doi: 10.1101/2023.06.05.543497. (PMID: 37333391)
References: Proc Natl Acad Sci U S A. 2017 Sep 12;114(37):E7812-E7821. (PMID: 28847947)
BMC Neurosci. 2007 Aug 02;8:63. (PMID: 17683525)
Trends Mol Med. 2019 Feb;25(2):96-111. (PMID: 30578089)
Nature. 2019 Apr;568(7751):249-253. (PMID: 30894749)
Proc Natl Acad Sci U S A. 1983 Dec;80(23):7357-61. (PMID: 6580651)
Nat Biotechnol. 2019 Jul;37(7):773-782. (PMID: 31061481)
Trends Genet. 2020 Nov;36(11):816-832. (PMID: 32839016)
Nat Neurosci. 2019 Feb;22(2):307-316. (PMID: 30643296)
Epigenetics. 2013 Mar;8(3):290-302. (PMID: 23426267)
Sci Rep. 2018 Jun 11;8(1):8868. (PMID: 29892006)
Clin Epigenetics. 2019 Mar 21;11(1):52. (PMID: 30898171)
J Transl Med. 2021 Jul 8;19(1):295. (PMID: 34238315)
Nucleic Acids Res. 2023 Jan 6;51(D1):D1188-D1195. (PMID: 36420891)
Cell. 2021 May 27;184(11):3022-3040.e28. (PMID: 33961781)
Front Cell Neurosci. 2013 Apr 23;7:44. (PMID: 23630462)
Neuroreport. 1997 Apr 14;8(6):1475-9. (PMID: 9172157)
J Neurosci. 2014 Sep 3;34(36):11929-47. (PMID: 25186741)
Science. 2015 Mar 6;347(6226):1138-42. (PMID: 25700174)
Nature. 1998 May 28;393(6683):386-9. (PMID: 9620804)
Mol Cell. 2001 Sep;8(3):719-25. (PMID: 11583633)
Proc Natl Acad Sci U S A. 2022 Nov 16;119(46):e2208804119. (PMID: 36343253)
Nat Neurosci. 2010 Jan;13(1):133-40. (PMID: 20023653)
Nat Rev Genet. 2019 Jul;20(7):417-431. (PMID: 30867571)
Database (Oxford). 2022 Sep 16;2022:. (PMID: 36124642)
J Biol Chem. 2017 Dec 29;292(52):21631-21642. (PMID: 29123026)
Genome Res. 2011 May;21(5):688-96. (PMID: 21467265)
Front Mol Neurosci. 2018 Dec 04;11:445. (PMID: 30564099)
Immunity. 2013 Jan 24;38(1):79-91. (PMID: 23273845)
Genome Res. 2021 Jan 19;:. (PMID: 33468551)
Genome Res. 2021 Jun 17;:. (PMID: 34140313)
Nat Genet. 2005 Aug;37(8):853-62. (PMID: 16007088)
Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):19359-19366. (PMID: 32719115)
Sci Rep. 2016 Jul 12;6:29396. (PMID: 27406855)
Geroscience. 2018 Feb;40(1):11-29. (PMID: 29327208)
Science. 2013 Aug 9;341(6146):1237905. (PMID: 23828890)
Nature. 2007 May 24;447(7143):425-32. (PMID: 17522676)
Science. 1975 Jan 24;187(4173):226-32. (PMID: 1111098)
Neuron. 2016 Dec 21;92(6):1181-1195. (PMID: 27939582)
Annu Rev Cell Dev Biol. 2018 Oct 6;34:265-288. (PMID: 30044650)
Nature. 2021 May;593(7859):440-444. (PMID: 33767446)
Cell. 2021 Jun 10;184(12):3222-3241.e26. (PMID: 34004146)
Protein Cell. 2019 Feb;10(2):87-103. (PMID: 30484118)
EMBO J. 2012 Nov 14;31(22):4318-33. (PMID: 23064151)
Proc Natl Acad Sci U S A. 2017 Apr 4;114(14):E2947-E2954. (PMID: 28320965)
Biology (Basel). 2014 Oct 22;3(4):670-723. (PMID: 25340699)
Nat Neurosci. 2019 Oct;22(10):1696-1708. (PMID: 31551601)
Genome Res. 2011 Oct;21(10):1592-600. (PMID: 21862626)
Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):6800-6. (PMID: 25739960)
J Neurosci. 2008 Jan 9;28(2):395-406. (PMID: 18184782)
Ann Rheum Dis. 2023 May;82(5):646-657. (PMID: 36898766)
Nat Commun. 2015 Feb 18;6:6363. (PMID: 25691127)
Nucleic Acids Res. 1994 Feb 25;22(4):695-6. (PMID: 8127720)
Genome Res. 2023 Jun;33(6):948-956. (PMID: 37442577)
Bioinformatics. 2022 May 26;38(11):3109-3112. (PMID: 35482479)
J Neurosci. 2014 Aug 20;34(34):11180-7. (PMID: 25143599)
Genome Biol. 2010;11(10):R106. (PMID: 20979621)
Mol Brain. 2017 Sep 4;10(1):43. (PMID: 28870203)
Curr Opin Genet Dev. 2020 Dec;65:84-90. (PMID: 32622340)
Neuropathol Appl Neurobiol. 2020 Feb;46(1):6-27. (PMID: 32056273)
Science. 2012 May 18;336(6083):934-7. (PMID: 22539555)
Annu Rev Med. 2019 Jan 27;70:151-166. (PMID: 30691368)
Nat Neurosci. 2016 Feb;19(2):335-46. (PMID: 26727548)
Nat Neurosci. 2007 Sep;10(9):1125-7. (PMID: 17660813)
Neuron. 2015 Jun 17;86(6):1369-84. (PMID: 26087164)
Epigenetics Chromatin. 2018 Jul 25;11(1):41. (PMID: 30045751)
Dev Neurosci. 2015;37(2):131-41. (PMID: 25721469)
BMC Genomics. 2018 Apr 4;19(1):234. (PMID: 29618320)
Genome Biol. 2012 Oct 03;13(10):R87. (PMID: 23034086)
Bioinformatics. 2015 Jul 15;31(14):2382-3. (PMID: 25765347)
Neuropharmacology. 2021 Feb 15;184:108370. (PMID: 33137342)
Mol Cell. 2010 May 28;38(4):576-89. (PMID: 20513432)
Nucleic Acids Res. 2011 Jul;39(12):5015-24. (PMID: 21378125)
Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):E265-74. (PMID: 21690374)
Transl Psychiatry. 2014 Sep 02;4:e433. (PMID: 25180572)
Nat Immunol. 2018 Jun;19(6):636-644. (PMID: 29777220)
Sci Adv. 2018 Sep 26;4(9):eaau6190. (PMID: 30263963)
Proc Natl Acad Sci U S A. 2016 Dec 27;113(52):15114-15119. (PMID: 27965390)
Cell Rep. 2017 Jan 24;18(4):1048-1061. (PMID: 28122230)
Neurobiol Aging. 2015 Aug;36(8):2443.e9-2443.e20. (PMID: 26002684)
Front Neurosci. 2020 Dec 01;14:603373. (PMID: 33335473)
J Biol Chem. 2006 Jun 9;281(23):15763-73. (PMID: 16606618)
Anal Chim Acta. 2014 Dec 10;852:212-7. (PMID: 25441900)
Acta Naturae. 2015 Apr-Jun;7(2):42-7. (PMID: 26085943)
Int J Neuropsychopharmacol. 2021 Nov 12;24(11):879-891. (PMID: 34214162)
Nat Rev Mol Cell Biol. 2010 Sep;11(9):607-20. (PMID: 20683471)
Cell. 2017 Nov 16;171(5):1151-1164.e16. (PMID: 29056337)
Sci Adv. 2020 Aug 28;6(35):eaba3200. (PMID: 32923624)
Nat Commun. 2021 Apr 1;12(1):2021. (PMID: 33795684)
Cell Rep. 2019 Oct 15;29(3):697-713.e8. (PMID: 31618637)
Nat Commun. 2022 Apr 5;13(1):1824. (PMID: 35383160)
Nature. 2021 Oct;598(7879):120-128. (PMID: 34616061)
Glia. 2021 Sep;69(9):2160-2177. (PMID: 34028094)
Nature. 2021 Oct;598(7879):129-136. (PMID: 34616068)
Brain Imaging Behav. 2019 Aug;13(4):963-972. (PMID: 29934819)
Nat Neurosci. 2016 Jan;19(1):102-10. (PMID: 26656643)
Nature. 2018 Oct;562(7727):367-372. (PMID: 30283141)
eNeuro. 2022 Mar 28;9(2):. (PMID: 35228310)
J Biol Chem. 2001 Jan 19;276(3):1881-8. (PMID: 11038359)
J Neurosci Res. 2014 May;92(5):658-70. (PMID: 24510599)
Nat Methods. 2017 Apr;14(4):407-410. (PMID: 28218898)
Nucleic Acids Res. 2014 Jan;42(1):109-27. (PMID: 24057217)
Nat Metab. 2022 Dec;4(12):1756-1774. (PMID: 36536134)
J Neurosci. 2015 Jul 22;35(29):10460-73. (PMID: 26203141)
Cancer Cell. 2014 Oct 13;26(4):577-90. (PMID: 25263941)
Commun Biol. 2022 Dec 1;5(1):1321. (PMID: 36456703)
Cell Rep. 2022 Mar 1;38(9):110435. (PMID: 35235798)
Cell Mol Immunol. 2022 May;19(5):650. (PMID: 35136226)
Nature. 2023 Apr;616(7955):113-122. (PMID: 36922587)
Philos Trans R Soc Lond B Biol Sci. 2014 Sep 26;369(1652):. (PMID: 25135973)
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7332-6. (PMID: 8692993)
Epigenomics. 2015;7(6):1051-73. (PMID: 25927341)
Cell Rep. 2018 Oct 2;25(1):1-9.e5. (PMID: 30282019)
Epigenetics Chromatin. 2016 Jun 29;9:25. (PMID: 27358653)
Proc Natl Acad Sci U S A. 2000 May 9;97(10):5237-42. (PMID: 10805783)
Nat Neurosci. 2022 Mar;25(3):306-316. (PMID: 35260865)
Genome Res. 2018 Aug;28(8):1147-1157. (PMID: 29970451)
Dis Model Mech. 2022 May 1;15(5):. (PMID: 35394029)
Cold Spring Harb Perspect Biol. 2015 Feb 02;7(2):a021808. (PMID: 25646382)
Genome Res. 2017 Mar;27(3):335-348. (PMID: 27965292)
Commun Biol. 2020 Nov 19;3(1):693. (PMID: 33214681)
Nat Protoc. 2011 Jan;6(1):56-68. (PMID: 21212783)
Curr Opin Neurobiol. 2012 Apr;22(2):294-300. (PMID: 22226994)
Gene. 2021 Feb 5;768:145306. (PMID: 33189799)
Science. 2017 Aug 11;357(6351):600-604. (PMID: 28798132)
Epigenomics. 2015;7(8):1259-74. (PMID: 26178076)
معلومات مُعتمدة: DP5 OD033443 United States OD NIH HHS; T32 AG052363 United States AG NIA NIH HHS; P30 EY021725 United States EY NEI NIH HHS; F31 AG064861 United States AG NIA NIH HHS; P30 AG050911 United States AG NIA NIH HHS; R01 AG059430 United States AG NIA NIH HHS; I01 BX003906 United States BX BLRD VA
فهرسة مساهمة: Keywords: Brain; Epigenomics; Genome regulation; Hydroxymethylation; Methylation; Regulatory elements
المشرفين على المادة: 9007-49-2 (DNA)
تواريخ الأحداث: Date Created: 20231112 Date Completed: 20231114 Latest Revision: 20240607
رمز التحديث: 20240607
مُعرف محوري في PubMed: PMC10642035
DOI: 10.1186/s13072-023-00522-6
PMID: 37953264
قاعدة البيانات: MEDLINE
الوصف
تدمد:1756-8935
DOI:10.1186/s13072-023-00522-6