The Lysine Acetyltransferase Activator Brpf1 Governs Dentate Gyrus Development through Neural Stem Cells and Progenitors

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Lysine acetylation refers to addition of the acetyl group to lysine residues after protein synthesis. Little is known about how this modification plays a role in the brain and neural stem cells. It is catalyzed by a group of enzymes known as lysine acetyltransferases. A novel epigenetic regulator called BRPF1 acts as a master activator of three different lysine acetyltransferases and also contains multiple structural domains for histone binding. In this study, we show that forebrain-specific inactivation of the mouse Brpf1 gene causes abnormal development of the dentate gyrus, a key component of the hippocampus. We trace the developmental origin to compromised neural stem cells and progenitors, and demonstrate that Brpf1 loss deregulates neuronal migration and cell cycle progression during development of the dentate gyrus. This is the first report on an epigenetic regulator whose loss has such a profound impact on the hippocampus, especially the dentate gyrus, a brain structure critical for learning, memory and adult neurogenesis.

Vyšlo v časopise: The Lysine Acetyltransferase Activator Brpf1 Governs Dentate Gyrus Development through Neural Stem Cells and Progenitors. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005034
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005034

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Zdroje

1. Kouzarides T (2000) Acetylation: a regulatory modification to rival phosphorylation? EMBO J 19 : 1176–1179. 10716917

2. Sterner DE, Berger SL (2000) Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev 64 : 435–459. 10839822

3. Yang XJ, Seto E (2008) Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol Cell 31 : 449–461. doi: 10.1016/j.molcel.2008.07.002 18722172

4. Kim SC, Sprung R, Chen Y, Xu Y, Ball H, et al. (2006) Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell 23 : 607–618. 16916647

5. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, et al. (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325 : 834–840. doi: 10.1126/science.1175371 19608861

6. Zhao S, Xu W, Jiang W, Yu W, Lin Y, et al. (2010) Regulation of cellular metabolism by protein lysine acetylation. Science 327 : 1000–1004. doi: 10.1126/science.1179689 20167786

7. Kaluarachchi Duffy S, Friesen H, Baryshnikova A, Lambert JP, Chong YT, et al. (2012) Exploring the yeast acetylome using functional genomics. Cell 149 : 936–948. doi: 10.1016/j.cell.2012.02.064 22579291

8. Zhang J, Sprung R, Pei J, Tan X, Kim S, et al. (2009) Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli. Mol Cell Proteomics 8 : 215–225. doi: 10.1074/mcp.M800187-MCP200 18723842

9. Wang Q, Zhang Y, Yang C, Xiong H, Lin Y, et al. (2010) Acetylation of metabolic enzymes coordinates carbon source utilization and metabolic flux. Science 327 : 1004–1007. doi: 10.1126/science.1179687 20167787

10. Weinert BT, Iesmantavicius V, Wagner SA, Scholz C, Gummesson B, et al. (2013) Acetyl-phosphate is a critical determinant of lysine acetylation in E. coli. Mol Cell 51 : 265–272. doi: 10.1016/j.molcel.2013.06.003 23830618

11. Roth SY, Denu JM, Allis CD (2001) Histone acetyltransferases. Annu Rev Biochem 70 : 81–120. 11395403

12. Carrozza MJ, Utley RT, Workman JL, Cote J (2003) The diverse functions of histone acetyltransferase complexes. Trends Genet 19 : 321–329. 12801725

13. Allis CD, Berger SL, Cote J, Dent S, Jenuwien T, et al. (2007) New nomenclature for chromatin-modifying enzymes. Cell 131 : 633–636. 18022353

14. Lafon A, Chang CS, Scott EM, Jacobson SJ, Pillus L (2007) MYST opportunities for growth control: yeast genes illuminate human cancer gene functions. Oncogene 26 : 5373–5384. 17694079

15. Rea S, Xouri G, Akhtar A (2007) Male absent on the first: from Drosophila to humans. Oncogene 26 : 5385–5394. 17694080

16. Yang XJ, Ullah M (2007) MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells. Oncogene 26 : 5408–5419. 17694082

17. Sykes SM, Mellert HS, Holbert MA, Li K, Marmorstein R, et al. (2006) Acetylation of the p53 DNA-binding domain regulates apoptosis induction. Mol Cell 24 : 841–851. 17189187

18. Tang Y, Luo J, Zhang W, Gu W (2006) Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis. Mol Cell 24 : 827–839. 17189186

19. Rokudai S, Laptenko O, Arnal SM, Taya Y, Kitabayashi I, et al. (2013) MOZ increases p53 acetylation and premature senescence through its complex formation with PML. Proc Natl Acad Sci U S A 110 : 3895–3900. doi: 10.1073/pnas.1300490110 23431171

20. Zheng H, Yang L, Peng L, Izumi V, Koomen J, et al. (2013) hMOF Acetylation of DBC1/CCAR2 Prevents Binding and Inhibition of SirT1. Mol Cell Biol epub.

21. Wang J, Chen J (2010) SIRT1 regulates autoacetylation and histone acetyltransferase activity of TIP60. J Biol Chem 285 : 11458–11464. doi: 10.1074/jbc.M109.087585 20100829

22. Lu L, Li L, Lv X, Wu XS, Liu DP, et al. (2011) Modulations of hMOF autoacetylation by SIRT1 regulate hMOF recruitment and activities on the chromatin. Cell Res 21 : 1182–1195. doi: 10.1038/cr.2011.71 21502975

23. Sun B, Guo S, Tang Q, Li C, Zeng R, et al. (2011) Regulation of the histone acetyltransferase activity of hMOF via autoacetylation of Lys274. Cell Res 21 : 1262–1266. doi: 10.1038/cr.2011.105 21691301

24. Peng L, Ling H, Yuan Z, Fang B, Bloom G, et al. (2012) SIRT1 negatively regulates the activities, functions, and protein levels of hMOF and TIP60. Mol Cell Biol 32 : 2823–2836. doi: 10.1128/MCB.00496-12 22586264

25. Yuan H, Rossetto D, Mellert H, Dang W, Srinivasan M, et al. (2012) MYST protein acetyltransferase activity requires active site lysine autoacetylation. EMBO J 31 : 58–70. doi: 10.1038/emboj.2011.382 22020126

26. Kaidi A, Jackson SP (2013) KAT5 tyrosine phosphorylation couples chromatin sensing to ATM signalling. Nature 498 : 70–74. doi: 10.1038/nature12201 23708966

27. Fullgrabe J, Lynch-Day MA, Heldring N, Li W, Struijk RB, et al. (2013) The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy. Nature 500 : 468–471. doi: 10.1038/nature12313 23863932

28. Yi C, Ma M, Ran L, Zheng J, Tong J, et al. (2012) Function and molecular mechanism of acetylation in autophagy regulation. Science 336 : 474–477. doi: 10.1126/science.1216990 22539722

29. Lin SY, Li TY, Liu Q, Zhang C, Li X, et al. (2012) GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to autophagy. Science 336 : 477–481. doi: 10.1126/science.1217032 22539723

30. Doyon Y, Cayrou C, Ullah M, Landry AJ, Cote V, et al. (2006) ING tumor suppressors are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell 21 : 51–64. 16387653

31. Ullah M, Pelletier N, Xiao L, Zhao SP, Wang K, et al. (2008) Molecular architecture of quartet MOZ/MORF histone acetyltransferase complexes. Mol Cell Biol 28 : 6828–6843. doi: 10.1128/MCB.01297-08 18794358

32. Lalonde M, Glass KC, Avakumov N, Joncas F, Saksouk N, et al. (2013) Exchange of associated factors directs a switch in HBO1 acetyltransferase histone tail specificity. Genes Dev 27 : 2009–2024. doi: 10.1101/gad.223396.113 24065767

33. Lubula MY, Eckenroth BE, Carlson S, Poplawski A, Chruszcz M, et al. (2014) Structural insights into recognition of acetylated histone ligands by the BRPF1 bromodomain. FEBS Lett 588 : 3844–3854. doi: 10.1016/j.febslet.2014.09.028 25281266

34. Vezzoli A, Bonadies N, Allen MD, Freund SM, Santiveri CM, et al. (2010) Molecular basis of histone H3K36me3 recognition by the PWWP domain of Brpf1. Nat Struct Mol Biol 17 : 617–619. doi: 10.1038/nsmb.1797 20400950

35. Wu H, Zeng H, Lam R, Tempel W, Amaya MF, et al. (2011) Structural and histone binding ability characterizations of human PWWP domains. PLoS One 6: e18919. doi: 10.1371/journal.pone.0018919 21720545

36. Chamberlin HM, Thomas JH (2000) The bromodomain protein LIN-49 and trithorax-related protein LIN-59 affect development and gene expression in Caenorhabditis elegans. Development 127 : 713–723. 10648230

37. Chang S, Johnston RJ Jr., Hobert O A transcriptional regulatory cascade that controls left/right asymmetry in chemosensory neurns of C. elegans. Genes Dev 17 : 2123–2137. 12952888

38. O’Meara MM, Zhang F, Hobert O (2010) Maintenance of neuronal laterality in Caenorhabditis elegans through MYST histone acetyltransferase complex components LSY-12, LSY-13 and LIN-49. Genetics 186 : 1497–1502. doi: 10.1534/genetics.110.123661 20923973

39. Laue K, Daujat S, Crump JG, Plaster N, Roehl HH, et al. (2008) The multidomain protein Brpf1 binds histones and is required for Hox gene expression and segmental identity. Development 135 : 1935–1946. doi: 10.1242/dev.017160 18469222

40. Hibiya K, Katsumoto T, Kondo T, Kitabayashi I, Kudo A (2009) Brpf1, a subunit of the MOZ histone acetyl transferase complex, maintains expression of anterior and posterior Hox genes for proper patterning of craniofacial and caudal skeletons. Dev Biol 329 : 176–190. doi: 10.1016/j.ydbio.2009.02.021 19254709

41. Mishima Y, Miyagi S, Saraya A, Negishi M, Endoh M, et al. (2011) The Hbo1-Brd1/Brpf2 complex is responsible for global acetylation of H3K14 and required for fetal liver erythropoiesis. Blood 118 : 2443–2453. doi: 10.1182/blood-2011-01-331892 21753189

42. Katsumoto T, Aikawa Y, Iwama A, Ueda S, Ichikawa H, et al. (2006) MOZ is essential for maintenance of hematopoietic stem cells. Genes Dev 20 : 1321–1330. 16702405

43. Thomas T, Corcoran LM, Gugasyan R, Dixon MP, Brodnicki T, et al. (2006) Monocytic leukemia zinc finger protein is essential for the development of long-term reconstituting hematopoietic stem cells. Genes Dev 20 : 1175–1186. 16651658

44. Deguchi K, Ayton PM, Carapeti M, Kutok JL, Snyder CS, et al. (2003) MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP. Cancer Cell 3 : 259–271. 12676584

45. Huntly BJ, Shigematsu H, Deguchi K, Lee BH, Mizuno S, et al. (2004) MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell 6 : 587–596. 15607963

46. Grasso CS, Wu YM, Robinson DR, Cao X, Dhanasekaran SM, et al. (2012) The mutational landscape of lethal castration-resistant prostate cancer. Nature 487 : 239–243. doi: 10.1038/nature11125 22722839

47. Lynch H, Wen H, Kim YC, Snyder C, Kinarsky Y, et al. (2013) Can Unknown Predisposition in Familial Breast Cancer be Family-Specific? Breast J 19 : 520–528. doi: 10.1111/tbj.12145 23800003

48. Kraft M, Cirstea IC, Voss AK, Thomas T, Goehring I, et al. (2011) Disruption of the histone acetyltransferase MYST4 leads to a Noonan syndrome-like phenotype and hyperactivated MAPK signaling in humans and mice. J Clin Invest 121 : 3479–3491. doi: 10.1172/JCI43428 21804188

49. Clayton-Smith J, O’Sullivan J, Daly S, Bhaskar S, Day R, et al. (2011) Whole-Exome-Sequencing Identifies Mutations in Histone Acetyltransferase Gene KAT6B in Individuals with the Say-Barber-Biesecker Variant of Ohdo Syndrome. Am J Hum Genet 89 : 675–681. doi: 10.1016/j.ajhg.2011.10.008 22077973

50. Simpson MA, Deshpande C, Dafou D, Vissers LE, Woollard WJ, et al. (2012) De Novo Mutations of the Gene Encoding the Histone Acetyltransferase KAT6B Cause Genitopatellar Syndrome. Am J Hum Genet 90 : 290–294. doi: 10.1016/j.ajhg.2011.11.024 22265017

51. Campeau PM, Kim JC, Lu JT, Schwartzentruber JA, Abdul-Rahman OA, et al. (2012) Mutations in KAT6B, Encoding a Histone Acetyltransferase, Cause Genitopatellar Syndrome. Am J Hum Genet 90 : 282–289. doi: 10.1016/j.ajhg.2011.11.023 22265014

52. Yu HC, Geiger EA, Medne L, Zackai EH, Shaikh TH (2014) An individual with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and additional features expands the phenotype associated with mutations in KAT6B. Am J Med Genet A 164 : 950–957.

53. Thomas T, Voss AK, Chowdhury K, Gruss P (2000) Querkopf, a MYST family histone acetyltransferase, is required for normal cerebral cortex development. Development 127 : 2537–2548. 10821753

54. Sheikh BN, Dixon MP, Thomas T, Voss AK (2012) Querkopf is a key marker of self-renewal and multipotency of adult neural stem cells. J Cell Sci 125 : 295–309. doi: 10.1242/jcs.077271 22331353

55. You L, Chen L, Panney J, Miao D, Yang XJ (2014) Expression atlas of the epigenetic regulator Brpf1 and its requirement for survival of mouse embryos. Epigenetics 9 : 860–872. doi: 10.4161/epi.28530 24646517

56. Gorski JA, Talley T, Qiu M, Puelles L, Rubenstein JL, et al. (2002) Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage. J Neurosci 22 : 6309–6314. 12151506

57. You L, Zou J, Zhao H, Bertos NR, Park M, et al. (2015) Deficiency of the chromatin regulator Brpf1 causes abnormal brain development. J Biol Chem: e-pub.

58. Forster E, Zhao S, Frotscher M (2006) Laminating the hippocampus. Nat Rev Neurosci 7 : 259–267. 16543914

59. Li G, Pleasure SJ (2007) Genetic regulation of dentate gyrus morphogenesis. Prog Brain Res 163 : 143–152. 17765716

60. Suto F, Tsuboi M, Kamiya H, Mizuno H, Kiyama Y, et al. (2007) Interactions between plexin-A2, plexin-A4, and semaphorin 6A control lamina-restricted projection of hippocampal mossy fibers. Neuron 53 : 535–547. 17296555

61. Favaro R, Valotta M, Ferri AL, Latorre E, Mariani J, et al. (2009) Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. Nat Neurosci 12 : 1248–1256. doi: 10.1038/nn.2397 19734891

62. Monaghan AP, Bock D, Gass P, Schwager A, Wolfer DP, et al. (1997) Defective limbic system in mice lacking the tailless gene. Nature 390 : 515–517. 9394001

63. Arnold SJ, Huang GJ, Cheung AF, Era T, Nishikawa S, et al. (2008) The T-box transcription factor Eomes/Tbr2 regulates neurogenesis in the cortical subventricular zone. Genes Dev 22 : 2479–2484. doi: 10.1101/gad.475408 18794345

64. Liu M, Pleasure SJ, Collins AE, Noebels JL, Naya FJ, et al. (2000) Loss of BETA2/NeuroD leads to malformation of the dentate gyrus and epilepsy. Proc Natl Acad Sci U S A 97 : 865–870. 10639171

65. Pellegrini M, Mansouri A, Simeone A, Boncinelli E, Gruss P (1996) Dentate gyrus formation requires Emx2. Development 122 : 3893–3898. 9012509

66. Galichet C, Guillemot F, Parras CM (2008) Neurogenin 2 has an essential role in development of the dentate gyrus. Development 135 : 2031–2041. doi: 10.1242/dev.015115 18448566

67. Tian C, Gong Y, Yang Y, Shen W, Wang K, et al. (2012) Foxg1 has an essential role in postnatal development of the dentate gyrus. J Neurosci 32 : 2931–2949. doi: 10.1523/JNEUROSCI.5240-11.2012 22378868

68. Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132 : 645–660. doi: 10.1016/j.cell.2008.01.033 18295581

69. Zhang CL, Zou Y, He W, Gage FH, Evans RM (2008) A role for adult TLX-positive neural stem cells in learning and behaviour. Nature 451 : 1004–1007. doi: 10.1038/nature06562 18235445

70. Hodge RD, Garcia AJ 3rd, Elsen GE, Nelson BR, Mussar KE, et al. (2013) Tbr2 expression in Cajal-Retzius cells and intermediate neuronal progenitors is required for morphogenesis of the dentate gyrus. J Neurosci 33 : 4165–4180. doi: 10.1523/JNEUROSCI.4185-12.2013 23447624

71. Simon R, Brylka H, Schwegler H, Venkataramanappa S, Andratschke J, et al. (2012) A dual function of Bcl11b/Ctip2 in hippocampal neurogenesis. EMBO J 31 : 2922–2936. doi: 10.1038/emboj.2012.142 22588081

72. Hodge RD, Nelson BR, Kahoud RJ, Yang R, Mussar KE, et al. (2012) Tbr2 is essential for hippocampal lineage progression from neural stem cells to intermediate progenitors and neurons. J Neurosci 32 : 6275–6287. doi: 10.1523/JNEUROSCI.0532-12.2012 22553033

73. Kriegstein A, Alvarez-Buylla A (2009) The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci 32 : 149–184. doi: 10.1146/annurev.neuro.051508.135600 19555289

74. Altman J, Bayer SA (1990) Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods. J Comp Neurol 301 : 365–381. 2262596

75. Yu DX, Marchetto MC, Gage FH (2014) How to make a hippocampal dentate gyrus granule neuron. Development 141 : 2366–2375. doi: 10.1242/dev.096776 24917496

76. Champagne N, Bertos NR, Pelletier N, Wang AH, Vezmar M, et al. (1999) Identification of a human histone acetyltransferase related to monocytic leukemia zinc finger protein. J Biol Chem 274 : 28528–28536. 10497217

77. Champagne N, Pelletier N, Yang XJ (2001) The monocytic leukemia zinc finger protein MOZ is a histone acetyltransferase. Oncogene 20 : 404–409. 11313971

78. Kitabayashi I, Aikawa Y, Nguyen LA, Yokoyama A, Ohki M (2001) Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein. EMBO J 20 : 7184–7196. 11742995

79. Kueh AJ, Dixon MP, Voss AK, Thomas T (2011) HBO1 is required for H3K14 acetylation and normal transcriptional activity during embryonic development. Mol Cell Biol 31 : 845–860. doi: 10.1128/MCB.00159-10 21149574

80. Perez-Campo FM, Costa G, Lie ALM, Stifani S, Kouskoff V, et al. (2014) MOZ-mediated repression of p16(INK) (4) (a) is critical for the self-renewal of neural and hematopoietic stem cells. Stem Cells 32 : 1591–1601. doi: 10.1002/stem.1606 24307508

81. Lavado A, Lagutin OV, Chow LM, Baker SJ, Oliver G (2010) Prox1 is required for granule cell maturation and intermediate progenitor maintenance during brain neurogenesis. PLoS Biol 8: e1000565. doi: 10.1371/journal.pbio.1000565 21203589

82. Han YG, Spassky N, Romaguera-Ros M, Garcia-Verdugo JM, Aguilar A, et al. (2008) Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells. Nat Neurosci 11 : 277–284. doi: 10.1038/nn2059 18297065

83. Greenbaum A, Hsu YM, Day RB, Schuettpelz LG, Christopher MJ, et al. (2013) CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature 495 : 227–230. doi: 10.1038/nature11926 23434756

84. Lu M, Grove EA, Miller RJ (2002) Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor. Proc Natl Acad Sci U S A 99 : 7090–7095. 11983855

85. Bagri A, Gurney T, He X, Zou YR, Littman DR, et al. (2002) The chemokine SDF1 regulates migration of dentate granule cells. Development 129 : 4249–4260. 12183377

86. Klein BJ, Lalonde ME, Cote J, Yang XJ, Kutateladze TG (2014) Crosstalk between epigenetic readers regulates the MOZ/MORF HAT complexes. Epigenetics 9 : 186–193. doi: 10.4161/epi.26792 24169304

87. Dong HW (2008) Allen Reference Altas, a digital brain atlas of the C57BL/6J male mouse. Hoboken, New Jersey: John Wiley & Sons, Inc.

88. Paxinos G, Franklin KBJ (2008) The Mouse Brain in Stereotaxic Coordinates: Academic Press.

89. Paxinos G, Halliday GM, Watson C, Koutcherov Y, Wang H (2006) Atlas of the Developing Mouse Brain at E17.5, P0 and P6, 1st Edition. Amsteram, Boston, Heidelberg, London, New York: Elsevier, Academic Press.

90. Schambra U (2008) Prenatal mouse brain atlas. New York: Springer.

91. Altman J, Bayer SA (1995) Atlas of prenatal rat brain development. Roca Raton: CRC Press.