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Cited by 15Epigenetics and DNA MethylationAdipokines, Inflammation, and Metabolic DiseasesPeroxisome Proliferator-Activated Receptors

TET2 is recruited by CREB to promote Cebpb, Cebpa, and Pparg transcription by facilitating hydroxymethylation during adipocyte differentiation

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Liu, Yunjia, He, Ting, Li, Zhuofang, Sun, Zhen, Wang, Shuai, Shen, Huanming, Hou, Lingfeng, Li, Shengnan +7 more·2023·iScience
DOI 10.1016/j.isci.2023.108312PMC PMC10663734
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Abstract

Ten-eleven translocation proteins (TETs) are dioxygenases that convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), an important epigenetic mark that regulates gene expression during development and differentiation. Here, we found that the TET2 expression was positively associated with adipogenesis. Further, in vitro and in vivo experiments showed that TET2 deficiency blocked adipogenesis by inhibiting the expression of the key transcription factors CCAAT/enhancer-binding protein beta (C/EBPβ), C/EBPα and peroxisome proliferator-activated receptor gamma (PPARγ). In addition, TET2 promoted 5hmC on the CpG islands (CGIs) of Cebpb , Cebpa and Pparg at the initial time point of their transcription, which requires the cAMP-responsive element-binding protein (CREB). At last, specific knockout of Tet2 in preadipocytes enabled mice to resist obesity and attenuated the obesity-associated insulin resistance. Together, TET2 is recruited by CREB to promote the expression of Cebpb , Cebpa and Pparg via 5hmC during adipogenesis and may be a potential therapeutic target for obesity and insulin resistance.

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  1. [1]Tahiliani M. Koh K.P. Shen Y. Pastor W.A. Bandukwala H. Brudno Y. Agarwal S. Iyer L.M. Liu D.R. Aravind L. Rao A. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1 Science 324 2009 930 935 10.1126/science.1170116 19372391 PMC2715015 · DOI · Paper page
  2. [2]Mellén M. Ayata P. Dewell S. Kriaucionis S. Heintz N. MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system Cell 151 2012 1417 1430 10.1016/j.cell.2012.11.022 23260135 PMC3653293 · DOI · Paper page
  3. [3]He B. Zhang C. Zhang X. Fan Y. Zeng H. Liu J. Meng H. Bai D. Peng J. Zhang Q. Tissue-specific 5-hydroxymethylcytosine landscape of the human genome Nat. Commun. 12 2021 4249 10.1038/s41467-021-24425-w 34253716 PMC8275684 · DOI
  4. [4]Ficz G. Branco M.R. Seisenberger S. Santos F. Krueger F. Hore T.A. Marques C.J. Andrews S. Reik W. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation Nature 473 2011 398 402 10.1038/nature10008 21460836 · DOI
  5. [5]Globisch D. Münzel M. Müller M. Michalakis S. Wagner M. Koch S. Brückl T. Biel M. Carell T. Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates PLoS One 5 2010 e15367 10.1371/journal.pone.0015367 PMC3009720 21203455 · DOI
  6. [6]Sérandour A.A. Avner S. Oger F. Bizot M. Percevault F. Lucchetti-Miganeh C. Palierne G. Gheeraert C. Barloy-Hubler F. Péron C.L. Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiation-associated enhancers Nucleic Acids Res. 40 2012 8255 8265 10.1093/nar/gks595 22730288 PMC3458548 · DOI
  7. [7]Fujiki K. Shinoda A. Kano F. Sato R. Shirahige K. Murata M. PPAR gamma-induced PARylation promotes local DNA demethylation by production of 5-hydroxymethylcytosine Nat. Commun. 4 2013 2262 10.1038/ncomms3262 23912449 · DOI · Paper page
  8. [8]Yoo Y. Park J.H. Weigel C. Liesenfeld D.B. Weichenhan D. Plass C. Seo D.G. Lindroth A.M. Park Y.J. TET-mediated hydroxymethylcytosine at the Pparγ locus is required for initiation of adipogenic differentiation Int. J. Obes. 41 2017 652 659 10.1038/ijo.2017.8 28100914 · DOI
  9. [9]Dubois-Chevalier J. Oger F. Dehondt H. Firmin F.F. Gheeraert C. Staels B. Lefebvre P. Eeckhoute J. A dynamic CTCF chromatin binding landscape promotes DNA hydroxymethylation and transcriptional induction of adipocyte differentiation Nucleic Acids Res. 42 2014 10943 10959 10.1093/nar/gku780 25183525 PMC4176165 · DOI
  10. [10]Park J. Lee D.H. Ham S. Oh J. Noh J.R. Lee Y.K. Park Y.J. Lee G. Han S.M. Han J.S. Targeted erasure of DNA methylation by TET3 drives adipogenic reprogramming and differentiation Nat. Metab. 4 2022 918 931 10.1038/s42255-022-00597-7 35788760 · DOI
  11. [11]Cao Z. Umek R.M. McKnight S.L. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells Genes Dev. 5 1991 1538 1552 10.1101/gad.5.9.1538 1840554 · DOI · Paper page
  12. [12]Macdougald O.A. Lane M.D. Transcriptional regulation of gene expression during adipocyte differentiation Annu. Rev. Biochem. 64 1995 345 373 10.1146/annurev.bi.64.070195.002021 7574486 · DOI
  13. [13]Yeh W.C. Cao Z. Classon M. McKnight S.L. Cascade regulation of terminal adipocyte differentiation by 3 members of the C/EBP family of leucine-zipper proteins Genes Dev. 9 1995 168 181 10.1101/gad.9.2.168 7531665 · DOI
  14. [14]Lane M.D. Tang Q.Q. Jiang M.S. Role of the CCAAT enhancer binding proteins (C/EBPs) in adipocyte differentiation Biochem. Biophys. Res. Commun. 266 1999 677 683 10603305
  15. [15]He T. Wang S. Li S. Shen H. Hou L. Liu Y. Wei Y. Xie F. Zhang Z. Zhao Z. Suppression of preadipocyte determination by SOX4 limits white adipocyte hyperplasia in obesity iScience 26 2023 106289 10.1016/j.isci.2023.106289 PMC10030912 36968079 · DOI
  16. [16]Tang Q.Q. Lane M.D. Adipogenesis: from stem cell to adipocyte Annu. Rev. Biochem. 81 2012 715 736 10.1146/annurev-biochem-052110-115718 22463691 · DOI
  17. [17]Zhang J.W. Klemm D.J. Vinson C. Lane M.D. Role of CREB in transcriptional regulation of CCAAT/enhancer-binding protein beta gene during adipogenesis J. Biol. Chem. 279 2004 4471 4478 10.1074/jbc.M311327200 14593102 · DOI
  18. [18]Tang Q.Q. Lane M.D. Activation and centromeric localization of CCAAT/enhancer-binding proteins during the mitotic clonal expansion of adipocyte differentiation Genes Dev. 13 1999 2231 2241 10.1101/gad.13.17.2231 10485846 PMC316997 · DOI
  19. [19]Niehof M. Manns M.P. Trautwein C. CREB controls LAP/C/EBP beta transcription Mol. Cell Biol. 17 1997 3600 3613 10.1128/mcb.17.7.3600 9199295 PMC232213 · DOI
  20. [20]Clarke S.L. Robinson C.E. Gimble J.M. CAAT/enhancer binding proteins directly modulate transcription from the peroxisome proliferator-activated receptor gamma 2 promoter Biochem. Biophys. Res. Commun. 240 1997 99 103 10.1006/bbrc.1997.7627 9367890 · DOI
  21. [21]Wu Z. Rosen E.D. Brun R. Hauser S. Adelmant G. Troy A.E. McKeon C. Darlington G.J. Spiegelman B.M. Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity Mol. Cell 3 1999 151 158 10.1016/s1097-2765(00)80306-8 10078198 · DOI
  22. [22]Graves R.A. Tontonoz P. Spiegelman B.M. Analysis of a tissue-specific enhancer: ARF6 regulates adipogenic gene expression Mol. Cell Biol. 12 1992 1202 1208 10.1128/mcb.12.3.1202 1545801 PMC369551 · DOI
  23. [23]Tontonoz P. Hu E. Graves R.A. Budavari A.I. Spiegelman B.M. mPPAR-gamma-2: tissue-specific regulator of an adipocyte enhancer Genes Dev. 8 1994 1224 1234 10.1101/gad.8.10.1224 7926726 · DOI
  24. [24]Christy R.J. Yang V.W. Ntambi J.M. Geiman D.E. Landschulz W.H. Friedman A.D. Nakabeppu Y. Kelly T.J. Lane M.D. Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes Genes Dev. 3 1989 1323 1335 10.1101/gad.3.9.1323 2606350 · DOI
  25. [25]Kaestner K.H. Christy R.J. Lane M.D. Mouse insulin-responsive glucose transporter gene: characterization of the gene and trans-activation by the CCAAT/enhancer binding protein Proc. Natl. Acad. Sci. USA 87 1990 251 255 10.1073/pnas.87.1.251 2404278 PMC53240 · DOI
  26. [26]Kershaw E.E. Schupp M. Guan H.-P. Gardner N.P. Lazar M.A. Flier J.S. PPARγ regulates adipose triglyceride lipase in adipocytes in vitro and in vivo Am. J. Physiol. Endocrinol. Metab. 293 2007 E1736 E1745 10.1152/ajpendo.00122.2007 17848638 PMC2819189 · DOI
  27. [27]Lin F.T. Lane M.D. CCAAT/enhancer binding protein alpha is sufficient to initiate the 3T3-L1 adipocyte differentiation program Proc. Natl. Acad. Sci. USA 91 1994 8757 8761 10.1073/pnas.91.19.8757 8090719 PMC44685 · DOI
  28. [28]Tang Q.-Q. Otto T.C. Lane M.D. CCAAT/enhancer-binding protein β is required for mitotic clonal expansion during adipogenesis Proc. Natl. Acad. Sci. USA 100 2003 850 855 10.1073/pnas.0337434100 12525691 PMC298690 · DOI
  29. [29]Wang N.D. Finegold M.J. Bradley A. Ou C.N. Abdelsayed S.V. Wilde M.D. Taylor L.R. Wilson D.R. Darlington G.J. Impaired energy homeostasis in C/EBP alpha knockout mice Science 269 1995 1108 1112 10.1126/science.7652557 7652557 · DOI · Paper page
  30. [30]Rosen E.D. Sarraf P. Troy A.E. Bradwin G. Moore K. Milstone D.S. Spiegelman B.M. Mortensen R.M. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro Mol. Cell 4 1999 611 617 10.1016/s1097-2765(00)80211-7 10549292 · DOI
  31. [31]Lee J.-E. Schmidt H. Lai B. Ge K. Transcriptional and Epigenomic Regulation of Adipogenesis Mol. Cell Biol. 39 2019 e00601-18 10.1128/mcb.00601-18 PMC6517598 30936246 · DOI
  32. [32]Farmer S.R. Transcriptional control of adipocyte formation Cell Metab. 4 2006 263 273 10.1016/j.cmet.2006.07.001 17011499 PMC1958996 · DOI
  33. [33]Wu X. Zhang Y. TET-mediated active DNA demethylation: mechanism, function and beyond Nat. Rev. Genet. 18 2017 517 534 10.1038/nrg.2017.33 28555658 · DOI · Paper page
  34. [34]Lisanti S. von Zglinicki T. Mathers J.C. Standardization and quality controls for the methylated DNA immunoprecipitation technique Epigenetics 7 2012 615 625 10.4161/epi.20028 22507898 · DOI
  35. [35]Niehof M. Kubicka S. Zender L. Manns M.P. Trautwein C. Autoregulation enables different pathways to control CCAAT/enhancer binding protein B (C/EBPB) transcription in vivo and in vitro J. Mol. Biol. 309 2001 855 868 10.1006/jmbi.2001.4708 11399064 · DOI
  36. [36]Yin X. Hu L. Xu Y. Structure and Function of TET Enzymes Adv. Exp. Med. Biol. 1389 2022 239 267 10.1007/978-3-031-11454-0_10 36350513 · DOI
  37. [37]Hu L. Li Z. Cheng J. Rao Q. Gong W. Liu M. Shi Y.G. Zhu J. Wang P. Xu Y. Crystal Structure of TET2-DNA Complex: Insight into TET-Mediated 5mC Oxidation Cell 155 2013 1545 1555 10.1016/j.cell.2013.11.020 24315485 · DOI
  38. [38]Park Y.-K. Ge K. Glucocorticoid Receptor Accelerates, but Is Dispensable for, Adipogenesis Mol. Cell Biol. 37 2017 e00260-16 10.1128/mcb.00260-16 MCB.00260-00216 PMC5214856 27777311 · DOI
  39. [39]Krueger K.C. Costa M.J. Du H. Feldman B.J. Characterization of Cre recombinase activity for in vivo targeting of adipocyte precursor cells Stem Cell Rep. 3 2014 1147 1158 10.1016/j.stemcr.2014.10.009 PMC4264060 25458893 · DOI
  40. [40]Berry R. Rodeheffer M.S. Characterization of the adipocyte cellular lineage in vivo Nat. Cell Biol. 15 2013 302 308 10.1038/ncb2696 23434825 PMC3721064 · DOI
  41. [41]Yildirim O. Li R. Hung J.H. Chen P.B. Dong X. Ee L.S. Weng Z. Rando O.J. Fazzio T.G. Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells Cell 147 2011 1498 1510 10.1016/j.cell.2011.11.054 22196727 PMC3252821 · DOI
  42. [42]Jones P.L. Veenstra G.J. Wade P.A. Vermaak D. Kass S.U. Landsberger N. Strouboulis J. Wolffe A.P. Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription Nat. Genet. 19 1998 187 191 10.1038/561 9620779 · DOI
  43. [43]Nan X. Ng H.H. Johnson C.A. Laherty C.D. Turner B.M. Eisenman R.N. Bird A. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex Nature 393 1998 386 389 10.1038/30764 9620804 · DOI · Paper page
  44. [44]Ng H.H. Zhang Y. Hendrich B. Johnson C.A. Turner B.M. Erdjument-Bromage H. Tempst P. Reinberg D. Bird A. MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex Nat. Genet. 23 1999 58 61 10.1038/12659 10471499 · DOI
  45. [45]Wade P.A. Gegonne A. Jones P.L. Ballestar E. Aubry F. Wolffe A.P. Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation Nat. Genet. 23 1999 62 66 10.1038/12664 10471500 · DOI
  46. [46]Kokura K. Kaul S.C. Wadhwa R. Nomura T. Khan M.M. Shinagawa T. Yasukawa T. Colmenares C. Ishii S. The Ski protein family is required for MeCP2-mediated transcriptional repression J. Biol. Chem. 276 2001 34115 34121 10.1074/jbc.M105747200 11441023 · DOI · Paper page
  47. [47]Rozenberg J.M. Shlyakhtenko A. Glass K. Rishi V. Myakishev M.V. FitzGerald P.C. Vinson C. All and only CpG containing sequences are enriched in promoters abundantly bound by RNA polymerase II in multiple tissues BMC Genom. 9 2008 67 10.1186/1471-2164-9-67 PMC2267717 18252004 · DOI
  48. [48]Deplus R. Delatte B. Schwinn M.K. Defrance M. Méndez J. Murphy N. Dawson M.A. Volkmar M. Putmans P. Calonne E. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS Embo J 32 2013 645 655 10.1038/emboj.2012.357 23353889 PMC3590984 · DOI
  49. [49]Fox K.E. Fankell D.M. Erickson P.F. Majka S.M. Crossno J.T. Jr. Klemm D.J. Depletion of cAMP-response element-binding protein/ATF1 inhibits adipogenic conversion of 3T3-L1 cells ectopically expressing CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBP beta, or PPAR gamma 2 J. Biol. Chem. 281 2006 40341 40353 10.1074/jbc.M605077200 17071615 · DOI
  50. [50]Rivers L.E. Young K.M. Rizzi M. Jamen F. Psachoulia K. Wade A. Kessaris N. Richardson W.D. PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice Nat. Neurosci. 11 2008 1392 1401 10.1038/nn.2220 18849983 PMC3842596 · DOI · Paper page
  51. [51]Zhao X. Dai J. Ma Y. Mi Y. Cui D. Ju G. Macklin W.B. Jin W. Dynamics of ten-eleven translocation hydroxylase family proteins and 5-hydroxymethylcytosine in oligodendrocyte differentiation Glia 62 2014 914 926 10.1002/glia.22649 24615693 · DOI
  52. [52]Xu Y. Wu F. Tan L. Kong L. Xiong L. Deng J. Barbera A.J. Zheng L. Zhang H. Huang S. Genome-wide Regulation of 5hmC, 5mC, and Gene Expression by Tet1 Hydroxylase in Mouse Embryonic Stem Cells Mol. Cell 42 2011 451 464 10.1016/j.molcel.2011.04.005 21514197 PMC3099128 · DOI
  53. [53]Adelmant G. Garg B.K. Tavares M. Card J.D. Marto J.A. Tandem Affinity Purification and Mass Spectrometry (TAP-MS) for the Analysis of Protein Complexes Curr. Protoc. Protein Sci. 96 2019 e84 10.1002/cpps.84 30706993 PMC6579647 · DOI

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Authors
Liu, Y., He, T., Li, Z., Sun, Z., Wang, S., Shen, H., Hou, L., Li, S., Wei, Y., Zhuo, B., Li, S., Zhou, C., Guo, H., Zhang, R., & Li, B.
Affiliations
Xiamen University (CN)
Corresponding author
  • Guo, Huiling
  • Zhang, Rui
  • Li, Boan
ORCID
Venue
iScience
Publisher
Elsevier BV
Published
2023-11
Volume
26
Issue
11
Pages
108312
ISSN
2589-0042 (ISSN-L)
DOI
10.1016/j.isci.2023.108312
PMC
PMC10663734
OpenAlex
W4387873411
Cited by
15
References
0
Citations by year
2026: 5 · 2025: 5 · 2024: 5
FWCI
1.34
Type
journal article
Language
en
Open access
Licence
Locations
  • iScience (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • State Administration of Foreign Experts Affairs (B06016)
  • National Natural Science Foundation of China (32071150, 3502Z20214001, 81700775, 81972458, 82103092)
  • Ministry of Education of the People's Republic of China
  • Ministry of Science and Technology of the People's Republic of China (2020YFA0112301)
  • Natural Science Foundation of Fujian Province (2022J05312)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords
TET2, 5-hydroxymethylcytosine, adipogenesis, CREB, C/EBPβ, C/EBPα, PPARγ, CpG islands, transcriptional regulation, obesity, insulin resistance, preadipocytes, epigenetic regulation

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