PRDM16 represses the type I interferon response in adipocytes to promote mitochondrial and thermogenic programing

EMBO Journal

Volumn 36, Issue 11, 2017, Pages 1528-1542

  Kissig, Megan ^a   Ishibashi, Jeff ^a   Harms, Matthew J ^a   Lim, Hee Woong ^a   Stine, Rachel R ^a   Won, Kyoung Jae ^a   Seale, Patrick ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

brown adipose; interferon regulatory factor; mitochondria; Prdm16; Ucp1

Indexed keywords

INTERFERON; INTERFERON REGULATORY FACTOR 1; STAT1 PROTEIN; STAT2 PROTEIN; STAT3 PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR PRDM16; UNCLASSIFIED DRUG; UNCOUPLING PROTEIN 1; DNA BINDING PROTEIN; IRF1 PROTEIN, MOUSE; PRDM16 PROTEIN, MOUSE; STAT1 PROTEIN, MOUSE; UCP1 PROTEIN, MOUSE;

ADIPOCYTE; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BROWN ADIPOSE TISSUE; CONTROLLED STUDY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; GENE; GENE EXPRESSION; GENE REPRESSION; IMMUNE RESPONSE; IN VITRO STUDY; IN VIVO STUDY; MALE; MITOCHONDRIAL GENE; MITOCHONDRION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; STAT1 GENE; THERMOGENESIS; WHITE ADIPOSE TISSUE; ANIMAL; ANTAGONISTS AND INHIBITORS; GENE EXPRESSION REGULATION; METABOLISM; PHYSIOLOGY;

ADIPOCYTES; ANIMALS; DNA-BINDING PROTEINS; GENE EXPRESSION REGULATION; INTERFERON REGULATORY FACTOR-1; INTERFERON TYPE I; MICE; MITOCHONDRIA; STAT1 TRANSCRIPTION FACTOR; THERMOGENESIS; TRANSCRIPTION FACTORS; UNCOUPLING PROTEIN 1;

EID: 85017514214     PISSN: 02614189     EISSN: 14602075     Source Type: Journal    
DOI: 10.15252/embj.201695588     Document Type: Article

References (74)

1. Abt MC, Osborne LC, Monticelli LA, Doering TA, Alenghat T, Sonnenberg GF, Paley MA, Antenus M, Williams KL, Erikson J, Wherry EJ, Artis D (2012) Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity 37: 158–170
2. Aguilo F, Avagyan S, Labar A, Sevilla A, Lee DF, Kumar P, Lemischka IR, Zhou BY, Snoeck HW (2011) Prdm16 is a physiologic regulator of hematopoietic stem cells. Blood 117: 5057–5066
3. Auffret J, Viengchareun S, Carre N, Denis RG, Magnan C, Marie PY, Muscat A, Feve B, Lombes M, Binart N (2012) Beige differentiation of adipose depots in mice lacking prolactin receptor protects against high-fat-diet-induced obesity. FASEB J 26: 3728–3737
4. Bromberg JF, Horvath CM, Wen Z, Schreiber RD, Darnell JE Jr (1996) Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma. Proc Natl Acad Sci USA 93: 7673–7678
5. Cederberg A, Gronning LM, Ahren B, Tasken K, Carlsson P, Enerback S (2001) FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance. Cell 106: 563–573
6. Chapgier A, Wynn RF, Jouanguy E, Filipe-Santos O, Zhang S, Feinberg J, Hawkins K, Casanova JL, Arkwright PD (2006) Human complete Stat-1 deficiency is associated with defective type I and II IFN responses in vitro but immunity to some low virulence viruses in vivo. J Immunol 176: 5078–5083
7. Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV, Clark NR, Ma'ayan A (2013) Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics 14: 128
8. Chuikov S, Levi BP, Smith ML, Morrison SJ (2010) Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress. Nat Cell Biol 12: 999–1006
9. Cohen P, Levy JD, Zhang Y, Frontini A, Kolodin DP, Svensson KJ, Lo JC, Zeng X, Ye L, Khandekar MJ, Wu J, Gunawardana SC, Banks AS, Camporez JP, Jurczak MJ, Kajimura S, Piston DW, Mathis D, Cinti S, Shulman GI et al (2014) Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 156: 304–316
10. Digby JE, Montague CT, Sewter CP, Sanders L, Wilkison WO, O'Rahilly S, Prins JB (1998) Thiazolidinedione exposure increases the expression of uncoupling protein 1 in cultured human preadipocytes. Diabetes 47: 138–141
11. Doody GM, Stephenson S, McManamy C, Tooze RM (2007) PRDM1/BLIMP-1 modulates IFN-gamma-dependent control of the MHC class I antigen-processing and peptide-loading pathway. J Immunol 179: 7614–7623
12. Dupuis S, Jouanguy E, Al-Hajjar S, Fieschi C, Al-Mohsen IZ, Al-Jumaah S, Yang K, Chapgier A, Eidenschenk C, Eid P, Al Ghonaium A, Tufenkeji H, Frayha H, Al-Gazlan S, Al-Rayes H, Schreiber RD, Gresser I, Casanova JL (2003) Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency. Nat Genet 33: 388–391
13. Eguchi J, Yan QW, Schones DE, Kamal M, Hsu CH, Zhang MQ, Crawford GE, Rosen ED (2008) Interferon regulatory factors are transcriptional regulators of adipogenesis. Cell Metab 7: 86–94
14. Eguchi J, Wang X, Yu S, Kershaw EE, Chiu PC, Dushay J, Estall JL, Klein U, Maratos-Flier E, Rosen ED (2011) Transcriptional control of adipose lipid handling by IRF4. Cell Metab 13: 249–259
15. Essers MA, Offner S, Blanco-Bose WE, Waibler Z, Kalinke U, Duchosal MA, Trumpp A (2009) IFNalpha activates dormant haematopoietic stem cells in vivo. Nature 458: 904–908
16. Feldmann HM, Golozoubova V, Cannon B, Nedergaard J (2009) UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab 9: 203–209
17. Fujita T, Kimura Y, Miyamoto M, Barsoumian EL, Taniguchi T (1989) Induction of endogenous IFN-alpha and IFN-beta genes by a regulatory transcription factor, IRF-1. Nature 337: 270–272
18. Ganal SC, Sanos SL, Kallfass C, Oberle K, Johner C, Kirschning C, Lienenklaus S, Weiss S, Staeheli P, Aichele P, Diefenbach A (2012) Priming of natural killer cells by nonmucosal mononuclear phagocytes requires instructive signals from commensal microbiota. Immunity 37: 171–186
19. Gough DJ, Messina NL, Hii L, Gould JA, Sabapathy K, Robertson AP, Trapani JA, Levy DE, Hertzog PJ, Clarke CJ, Johnstone RW (2010) Functional crosstalk between type I and II interferon through the regulated expression of STAT1. PLoS Biol 8: e1000361
20. Guerra C, Koza RA, Yamashita H, Walsh K, Kozak LP (1998) Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J Clin Invest 102: 412–420
21. Hamilton JA, Whitty GA, Kola I, Hertzog PJ (1996) Endogenous IFN-alpha beta suppresses colony-stimulating factor (CSF)-1-stimulated macrophage DNA synthesis and mediates inhibitory effects of lipopolysaccharide and TNF-alpha. J Immunol 156: 2553–2557
22. Harada H, Willison K, Sakakibara J, Miyamoto M, Fujita T, Taniguchi T (1990) Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated. Cell 63: 303–312
23. Harms MJ, Ishibashi J, Wang W, Lim HW, Goyama S, Sato T, Kurokawa M, Won KJ, Seale P (2014) Prdm16 is required for the maintenance of brown adipocyte identity and function in adult mice. Cell Metab 19: 593–604
24. Harms MJ, Lim HW, Ho Y, Shapira SN, Ishibashi J, Rajakumari S, Steger DJ, Lazar MA, Won KJ, Seale P (2015) PRDM16 binds MED1 and controls chromatin architecture to determine a brown fat transcriptional program. Genes Dev 29: 298–307
25. Hata N, Sato M, Takaoka A, Asagiri M, Tanaka N, Taniguchi T (2001) Constitutive IFN-alpha/beta signal for efficient IFN-alpha/beta gene induction by virus. Biochem Biophys Res Commun 285: 518–525
26. Hida S, Ogasawara K, Sato K, Abe M, Takayanagi H, Yokochi T, Sato T, Hirose S, Shirai T, Taki S, Taniguchi T (2000) CD8(+) T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-alpha/beta signaling. Immunity 13: 643–655
27. Honda K, Yanai H, Takaoka A, Taniguchi T (2005) Regulation of the type I IFN induction: a current view. Int Immunol 17: 1367–1378
28. Horvath CM, Stark GR, Kerr IM, Darnell JE Jr (1996) Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex. Mol Cell Biol 16: 6957–6964
29. Hwang SY, Hertzog PJ, Holland KA, Sumarsono SH, Tymms MJ, Hamilton JA, Whitty G, Bertoncello I, Kola I (1995) A null mutation in the gene encoding a type I interferon receptor component eliminates antiproliferative and antiviral responses to interferons alpha and beta and alters macrophage responses. Proc Natl Acad Sci USA 92: 11284–11288
30. Iida S, Chen W, Nakadai T, Ohkuma Y, Roeder RG (2015) PRDM16 enhances nuclear receptor-dependent transcription of the brown fat-specific Ucp1 gene through interactions with Mediator subunit MED1. Genes Dev 29: 308–321
31. Ishibashi J, Seale P (2015) Functions of Prdm16 in thermogenic fat cells. Temperature 2: 65–72
32. Kajimura S, Seale P, Tomaru T, Erdjument-Bromage H, Cooper MP, Ruas JL, Chin S, Tempst P, Lazar MA, Spiegelman BM (2008) Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes Dev 22: 1397–1409
33. Kajimura S, Seale P, Kubota K, Lunsford E, Frangioni JV, Gygi SP, Spiegelman BM (2009) Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature 460: 1154–1158
34. Kawashima T, Kosaka A, Yan H, Guo Z, Uchiyama R, Fukui R, Kaneko D, Kumagai Y, You DJ, Carreras J, Uematsu S, Jang MH, Takeuchi O, Kaisho T, Akira S, Miyake K, Tsutsui H, Saito T, Nishimura I, Tsuji NM (2013) Double-stranded RNA of intestinal commensal but not pathogenic bacteria triggers production of protective interferon-beta. Immunity 38: 1187–1197
35. Kim PG, Canver MC, Rhee C, Ross SJ, Harriss JV, Tu HC, Orkin SH, Tucker HO, Daley GQ (2016) Interferon-alpha signaling promotes embryonic HSC maturation. Blood 128: 204–216
36. Kimura T, Nakayama K, Penninger J, Kitagawa M, Harada H, Matsuyama T, Tanaka N, Kamijo R, Vilcek J, Mak TW, Taniguchi T (1994) Involvement of the IRF-1 transcription factor in antiviral responses to interferons. Science 264: 1921–1924
37. Klingenberg M, Echtay KS, Bienengraeber M, Winkler E, Huang SG (1999) Structure-function relationship in UCP1. Int J Obes Relat Metab Disord 23(Suppl. 6): S24–S29
38. Kong X, Banks A, Liu T, Kazak L, Rao RR, Cohen P, Wang X, Yu S, Lo JC, Tseng YH, Cypess AM, Xue R, Kleiner S, Kang S, Spiegelman BM, Rosen ED (2014) IRF4 is a key thermogenic transcriptional partner of PGC-1alpha. Cell 158: 69–83
39. Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, Koplev S, Jenkins SL, Jagodnik KM, Lachmann A, McDermott MG, Monteiro CD, Gundersen GW, Ma'ayan A (2016) Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res 44: W90–W97
40. Kumari M, Wang X, Lantier L, Lyubetskaya A, Eguchi J, Kang S, Tenen D, Roh HC, Kong X, Kazak L, Ahmad R, Rosen ED (2016) IRF3 promotes adipose inflammation and insulin resistance and represses browning. J Clin Invest 126: 2839–2854
41. Kuo TC, Calame KL (2004) B lymphocyte-induced maturation protein (Blimp)-1, IFN regulatory factor (IRF)-1, and IRF-2 can bind to the same regulatory sites. J Immunol 173: 5556–5563
42. Lee K, Um SH, Rhee DK, Pyo S (2016) Interferon-alpha inhibits adipogenesis via regulation of JAK/STAT1 signaling. Biochim Biophys Acta 1860: 2416–2427
43. Lei Q, Liu X, Fu H, Sun Y, Wang L, Xu G, Wang W, Yu Z, Liu C, Li P, Feng J, Li G, Wu M (2016) miR-101 reverses hypomethylation of the PRDM16 promoter to disrupt mitochondrial function in astrocytoma cells. Oncotarget 7: 5007–5022
44. Leung S, Qureshi SA, Kerr IM, Darnell JE Jr, Stark GR (1995) Role of STAT2 in the alpha interferon signaling pathway. Mol Cell Biol 15: 1312–1317
45. Lewis JA, Huq A, Najarro P (1996) Inhibition of mitochondrial function by interferon. J Biol Chem 271: 13184–13190
46. Li X, Wang J, Jiang Z, Guo F, Soloway PD, Zhao R (2015) Role of PRDM16 and its PR domain in the epigenetic regulation of myogenic and adipogenic genes during transdifferentiation of C2C12 cells. Gene 570: 191–198
47. Luchsinger LL, de Almeida MJ, Corrigan DJ, Mumau M, Snoeck HW (2016) Mitofusin 2 maintains haematopoietic stem cells with extensive lymphoid potential. Nature 529: 528–531
48. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ (2009) Cold-activated brown adipose tissue in healthy men. N Engl J Med 360: 1500–1508
49. Meraz MA, White JM, Sheehan KC, Bach EA, Rodig SJ, Dighe AS, Kaplan DH, Riley JK, Greenlund AC, Campbell D, Carver-Moore K, DuBois RN, Clark R, Aguet M, Schreiber RD (1996) Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell 84: 431–442
50. Moisan A, Lee YK, Zhang JD, Hudak CS, Meyer CA, Prummer M, Zoffmann S, Truong HH, Ebeling M, Kiialainen A, Gerard R, Xia F, Schinzel RT, Amrein KE, Cowan CA (2015) White-to-brown metabolic conversion of human adipocytes by JAK inhibition. Nat Cell Biol 17: 57–67
51. Mould AW, Morgan MA, Nelson AC, Bikoff EK, Robertson EJ (2015) Blimp1/Prdm1 functions in opposition to Irf1 to maintain neonatal tolerance during postnatal intestinal maturation. PLoS Genet 11: e1005375
52. Nishikata I, Sasaki H, Iga M, Tateno Y, Imayoshi S, Asou N, Nakamura T, Morishita K (2003) A novel EVI1 gene family, MEL1, lacking a PR domain (MEL1S) is expressed mainly in t(1;3)(p36;q21)-positive AML and blocks G-CSF-induced myeloid differentiation. Blood 102: 3323–3332
53. Ohno H, Shinoda K, Spiegelman BM, Kajimura S (2012) PPARgamma agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein. Cell Metab 15: 395–404
54. Ohno H, Shinoda K, Ohyama K, Sharp LZ, Kajimura S (2013) EHMT1 controls brown adipose cell fate and thermogenesis through the PRDM16 complex. Nature 504: 163–167
55. Park C, Li S, Cha E, Schindler C (2000) Immune response in Stat2 knockout mice. Immunity 13: 795–804
56. Petrovic N, Shabalina IG, Timmons JA, Cannon B, Nedergaard J (2008) Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a PPARgamma agonist. Am J Physiol Endocrinol Metab 295: E287–E296
57. Pinheiro I, Margueron R, Shukeir N, Eisold M, Fritzsch C, Richter FM, Mittler G, Genoud C, Goyama S, Kurokawa M, Son J, Reinberg D, Lachner M, Jenuwein T (2012) Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity. Cell 150: 948–960
58. Rajakumari S, Wu J, Ishibashi J, Lim HW, Giang AH, Won KJ, Reed RR, Seale P (2013) EBF2 determines and maintains brown adipocyte identity. Cell Metab 17: 562–574
59. Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K, Kawai Y, Tsujisaki M (2009) High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 58: 1526–1531
60. Sato M, Suemori H, Hata N, Asagiri M, Ogasawara K, Nakao K, Nakaya T, Katsuki M, Noguchi S, Tanaka N, Taniguchi T (2000) Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-alpha/beta gene induction. Immunity 13: 539–548
61. Sato T, Onai N, Yoshihara H, Arai F, Suda T, Ohteki T (2009) Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon-dependent exhaustion. Nat Med 15: 696–700
62. Schafer SL, Lin R, Moore PA, Hiscott J, Pitha PM (1998) Regulation of type I interferon gene expression by interferon regulatory factor-3. J Biol Chem 273: 2714–2720
63. Seale P, Kajimura S, Yang W, Chin S, Rohas LM, Uldry M, Tavernier G, Langin D, Spiegelman BM (2007) Transcriptional control of brown fat determination by PRDM16. Cell Metab 6: 38–54
64. Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scime A, Devarakonda S, Conroe HM, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR, Spiegelman BM (2008) PRDM16 controls a brown fat/skeletal muscle switch. Nature 454: 961–967
65. Seale P, Conroe HM, Estall J, Kajimura S, Frontini A, Ishibashi J, Cohen P, Cinti S, Spiegelman BM (2011) Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest 121: 96–105
66. Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA, Mikkelsen TS, Heckl D, Ebert BL, Root DE, Doench JG, Zhang F (2014) Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343: 84–87
67. Shan B, Vazquez E, Lewis JA (1990) Interferon selectively inhibits the expression of mitochondrial genes: a novel pathway for interferon-mediated responses. EMBO J 9: 4307–4314
68. Tai TA, Jennermann C, Brown KK, Oliver BB, MacGinnitie MA, Wilkison WO, Brown HR, Lehmann JM, Kliewer SA, Morris DC, Graves RA (1996) Activation of the nuclear receptor peroxisome proliferator-activated receptor gamma promotes brown adipocyte differentiation. J Biol Chem 271: 29909–29914
69. Tovey MG, Streuli M, Gresser I, Gugenheim J, Blanchard B, Guymarho J, Vignaux F, Gigou M (1987) Interferon messenger RNA is produced constitutively in the organs of normal individuals. Proc Natl Acad Sci USA 84: 5038–5042
70. Vogel SN, Fertsch D (1984) Endogenous interferon production by endotoxin-responsive macrophages provides an autostimulatory differentiation signal. Infect Immun 45: 417–423
71. Wang XA, Zhang R, Zhang S, Deng S, Jiang D, Zhong J, Yang L, Wang T, Hong S, Guo S, She ZG, Zhang XD, Li H (2013) Interferon regulatory factor 7 deficiency prevents diet-induced obesity and insulin resistance. Am J Physiol Endocrinol Metab 305: E485–E495
72. Xu L, Zhou X, Wang W, Wang Y, Yin Y, van der Laan LJ, Sprengers D, Metselaar HJ, Peppelenbosch MP, Pan Q (2016) IFN regulatory factor 1 restricts hepatitis E virus replication by activating STAT1 to induce antiviral IFN-stimulated genes. FASEB J 30: 3352–3367
73. Yu Q, Katlinskaya YV, Carbone CJ, Zhao B, Katlinski KV, Zheng H, Guha M, Li N, Chen Q, Yang T, Lengner CJ, Greenberg RA, Johnson FB, Fuchs SY (2015) DNA-damage-induced type I interferon promotes senescence and inhibits stem cell function. Cell Rep 11: 785–797
74. Zhou B, Wang J, Lee SY, Xiong J, Bhanu N, Guo Q, Ma P, Sun Y, Rao RC, Garcia BA, Hess JL, Dou Y (2016) PRDM16 suppresses MLL1r leukemia via intrinsic histone methyltransferase activity. Mol Cell 62: 222–236