KDM6 Demethylase Independent Loss of Histone H3 Lysine 27 Trimethylation during Early Embryonic Development
H3K27me3 represses developmental genes at initial embryonic stages. The KDM6 family, comprised of UTX and JMJD3, are the only known proteins that demethylate H3K27me3 and they are hypothesized to catalyze the rapid removal of repressive chromatin in early mammalian development. However, we report that male embryos carrying mutations in both Utx and Jmjd3 survive to term and appear phenotypically normal at mid-gestation. We utilize several cell culture models to demonstrate that H3K27me3 is lost from repressed promoters in the absence of active KDM6 demethylation. Our data indicate that KDM6 H3K27me3 demethylation is not essential in the early embryo and that H3K27me3 loss from developmental genes occurs via novel mechanisms.
Vyšlo v časopise:
KDM6 Demethylase Independent Loss of Histone H3 Lysine 27 Trimethylation during Early Embryonic Development. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004507
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1004507
Souhrn
H3K27me3 represses developmental genes at initial embryonic stages. The KDM6 family, comprised of UTX and JMJD3, are the only known proteins that demethylate H3K27me3 and they are hypothesized to catalyze the rapid removal of repressive chromatin in early mammalian development. However, we report that male embryos carrying mutations in both Utx and Jmjd3 survive to term and appear phenotypically normal at mid-gestation. We utilize several cell culture models to demonstrate that H3K27me3 is lost from repressed promoters in the absence of active KDM6 demethylation. Our data indicate that KDM6 H3K27me3 demethylation is not essential in the early embryo and that H3K27me3 loss from developmental genes occurs via novel mechanisms.
Zdroje
1. AzuaraV, PerryP, SauerS, SpivakovM, JorgensenHF, et al. (2006) Chromatin signatures of pluripotent cell lines. Nat Cell Biol 8: 532–538.
2. BernsteinBE, MikkelsenTS, XieX, KamalM, HuebertDJ, et al. (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125: 315–326.
3. KuM, KocheRP, RheinbayE, MendenhallEM, EndohM, et al. (2008) Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genet 4: e1000242.
4. MikkelsenTS, KuM, JaffeDB, IssacB, LiebermanE, et al. (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448: 553–560.
5. Rugg-GunnPJ, CoxBJ, RalstonA, RossantJ (2010) Distinct histone modifications in stem cell lines and tissue lineages from the early mouse embryo. Proc Natl Acad Sci U S A 107: 10783–10790.
6. SachsM, OnoderaC, BlaschkeK, EbataKT, SongJS, et al. (2013) Bivalent Chromatin Marks Developmental Regulatory Genes in the Mouse Embryonic Germline In Vivo. Cell Rep 3: 1777–84 doi: 10.1016/j.celrep.2013.04.032
7. HammoudSS, NixDA, ZhangH, PurwarJ, CarrellDT, et al. (2009) Distinctive chromatin in human sperm packages genes for embryo development. Nature 460: 473–478.
8. LindemanLC, AndersenIS, ReinerAH, LiN, AanesH, et al. (2011) Prepatterning of developmental gene expression by modified histones before zygotic genome activation. Dev Cell 21: 993–1004.
9. DahlJA, ReinerAH, KlunglandA, WakayamaT, CollasP (2010) Histone H3 lysine 27 methylation asymmetry on developmentally-regulated promoters distinguish the first two lineages in mouse preimplantation embryos. PLoS One 5: e9150.
10. AlderO, LavialF, HelnessA, BrookesE, PinhoS, et al. (2010) Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment. Development 137: 2483–2492.
11. CuiK, ZangC, RohTY, SchonesDE, ChildsRW, et al. (2009) Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation. Cell Stem Cell 4: 80–93.
12. van ArensbergenJ, Garcia-HurtadoJ, MoranI, MaestroMA, XuX, et al. (2010) Derepression of Polycomb targets during pancreatic organogenesis allows insulin-producing beta-cells to adopt a neural gene activity program. Genome Res 20: 722–732.
13. RohTY, CuddapahS, CuiK, ZhaoK (2006) The genomic landscape of histone modifications in human T cells. Proc Natl Acad Sci U S A 103: 15782–15787.
14. ZhaoXD, HanX, ChewJL, LiuJ, ChiuKP, et al. (2007) Whole-genome mapping of histone H3 Lys4 and 27 trimethylations reveals distinct genomic compartments in human embryonic stem cells. Cell Stem Cell 1: 286–298.
15. PanG, TianS, NieJ, YangC, RuottiV, et al. (2007) Whole-genome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells. Cell Stem Cell 1: 299–312.
16. WangAH, ZareH, MousaviK, WangC, MoravecCE, et al. (2013) The histone chaperone Spt6 coordinates histone H3K27 demethylation and myogenesis. EMBO J 32: 1075–1086.
17. KartikasariAE, ZhouJX, KanjiMS, ChanDN, SinhaA, et al. (2013) The histone demethylase Jmjd3 sequentially associates with the transcription factors Tbx3 and Eomes to drive endoderm differentiation. EMBO J 32: 1393–1408.
18. RamadossS, ChenX, WangCY (2012) Histone demethylase KDM6B promotes epithelial-mesenchymal transition. J Biol Chem 287: 44508–44517.
19. JiangW, WangJ, ZhangY (2012) Histone H3K27me3 demethylases KDM6A and KDM6B modulate definitive endoderm differentiation from human ESCs by regulating WNT signaling pathway. Cell Res 23: 122–130.
20. WangJK, TsaiMC, PoulinG, AdlerAS, ChenS, et al. (2010) The histone demethylase UTX enables RB-dependent cell fate control. Genes Dev 24: 327–332.
21. SeenundunS, RampalliS, LiuQC, AzizA, PaliiC, et al. (2010) UTX mediates demethylation of H3K27me3 at muscle-specific genes during myogenesis. EMBO J 29: 1401–1411.
22. BurgoldT, SpreaficoF, De SantaF, TotaroMG, ProsperiniE, et al. (2008) The histone H3 lysine 27-specific demethylase Jmjd3 is required for neural commitment. PLoS One 3: e3034.
23. SatohT, TakeuchiO, VandenbonA, YasudaK, TanakaY, et al. (2010) The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat Immunol 11: 936–944.
24. SenGL, WebsterDE, BarraganDI, ChangHY, KhavariPA (2008) Control of differentiation in a self-renewing mammalian tissue by the histone demethylase JMJD3. Genes Dev 22: 1865–1870.
25. BarradasM, AndertonE, AcostaJC, LiS, BanitoA, et al. (2009) Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS. Genes Dev 23: 1177–1182.
26. AggerK, CloosPA, RudkjaerL, WilliamsK, AndersenG, et al. (2009) The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence. Genes Dev 23: 1171–1176.
27. LanF, BaylissPE, RinnJL, WhetstineJR, WangJK, et al. (2007) A histone H3 lysine 27 demethylase regulates animal posterior development. Nature 449: 689–694.
28. De SantaF, TotaroMG, ProsperiniE, NotarbartoloS, TestaG, et al. (2007) The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing. Cell 130: 1083–1094.
29. AggerK, CloosPA, ChristensenJ, PasiniD, RoseS, et al. (2007) UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature 449: 731–734.
30. LeeMG, VillaR, TrojerP, NormanJ, YanKP, et al. (2007) Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination. Science 318: 447–450.
31. ShpargelKB, SengokuT, YokoyamaS, MagnusonT (2012) UTX and UTY demonstrate histone demethylase-independent function in mouse embryonic development. PLoS Genet 8: e1002964.
32. WangC, LeeJE, ChoYW, XiaoY, JinQ, et al. (2012) UTX regulates mesoderm differentiation of embryonic stem cells independent of H3K27 demethylase activity. Proc Natl Acad Sci U S A 109: 15324–15329.
33. HongS, ChoYW, YuLR, YuH, VeenstraTD, et al. (2007) Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases. Proc Natl Acad Sci U S A 104: 18439–18444.
34. WalportLJ, HopkinsonRJ, VollmarM, MaddenSK, GileadiC, et al. (2014) Human UTY(KDM6C) is a Male-Specific N-Methyl Lysyl-Demethylase. J Biol Chem 289: 18302–18313.
35. BurgoldT, VoituronN, CaganovaM, TripathiPP, MenuetC, et al. (2012) The H3K27 demethylase JMJD3 is required for maintenance of the embryonic respiratory neuronal network, neonatal breathing, and survival. Cell Rep 2: 1244–1258.
36. ChamberlainSJ, YeeD, MagnusonT (2008) Polycomb repressive complex 2 is dispensable for maintenance of embryonic stem cell pluripotency. Stem Cells 26: 1496–1505.
37. FaustC, SchumacherA, HoldenerB, MagnusonT (1995) The eed mutation disrupts anterior mesoderm production in mice. Development 121: 273–285.
38. PasiniD, BrackenAP, JensenMR, Lazzerini DenchiE, HelinK (2004) Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity. EMBO J 23: 4061–4071.
39. O'CarrollD, ErhardtS, PaganiM, BartonSC, SuraniMA, et al. (2001) The polycomb-group gene Ezh2 is required for early mouse development. Mol Cell Biol 21: 4330–4336.
40. CopurO, MullerJ (2013) The histone H3-K27 demethylase Utx regulates HOX gene expression in Drosophila in a temporally restricted manner. Development 140: 3478–3485.
41. HayashiS, McMahonAP (2002) Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse. Dev Biol 244: 305–318.
42. WalkerE, ChangWY, HunkapillerJ, CagneyG, GarchaK, et al. (2010) Polycomb-like 2 associates with PRC2 and regulates transcriptional networks during mouse embryonic stem cell self-renewal and differentiation. Cell Stem Cell 6: 153–166.
43. ZhangH, BradleyA (1996) Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development 122: 2977–2986.
44. MeyersEN, LewandoskiM, MartinGR (1998) An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination. Nat Genet 18: 136–141.
45. MolkentinJD, LinQ, DuncanSA, OlsonEN (1997) Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev 11: 1061–1072.
46. MorriseyEE, TangZ, SigristK, LuMM, JiangF, et al. (1998) GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo. Genes Dev 12: 3579–3590.
47. ArnoldSJ, HofmannUK, BikoffEK, RobertsonEJ (2008) Pivotal roles for eomesodermin during axis formation, epithelium-to-mesenchyme transition and endoderm specification in the mouse. Development 135: 501–511.
48. RussAP, WattlerS, ColledgeWH, AparicioSA, CarltonMB, et al. (2000) Eomesodermin is required for mouse trophoblast development and mesoderm formation. Nature 404: 95–99.
49. HerrmannBG (1991) Expression pattern of the Brachyury gene in whole-mount TWis/TWis mutant embryos. Development 113: 913–917.
50. WinnierG, BlessingM, LaboskyPA, HoganBL (1995) Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 9: 2105–2116.
51. LiuP, WakamiyaM, SheaMJ, AlbrechtU, BehringerRR, et al. (1999) Requirement for Wnt3 in vertebrate axis formation. Nat Genet 22: 361–365.
52. CarverEA, JiangR, LanY, OramKF, GridleyT (2001) The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition. Mol Cell Biol 21: 8184–8188.
53. XieW, SchultzMD, ListerR, HouZ, RajagopalN, et al. (2013) Epigenomic analysis of multilineage differentiation of human embryonic stem cells. Cell 153: 1134–1148.
54. GiffordCA, ZillerMJ, GuH, TrapnellC, DonagheyJ, et al. (2013) Transcriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells. Cell 153: 1149–1163.
55. MansourAA, GafniO, WeinbergerL, ZviranA, AyyashM, et al. (2012) The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming. Nature 488: 409–413.
56. WelsteadGG, CreyghtonMP, BilodeauS, ChengAW, MarkoulakiS, et al. (2012) X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex-specific manner. Proc Natl Acad Sci U S A 109: 13004–13009.
57. Morales TorresC, LaugesenA, HelinK (2013) Utx is required for proper induction of ectoderm and mesoderm during differentiation of embryonic stem cells. PLoS One 8: e60020.
58. ShahhoseiniM, TaghizadehZ, HatamiM, BaharvandH (2013) Retinoic acid dependent histone 3 demethylation of the clustered HOX genes during neural differentiation of human embryonic stem cells. Biochem Cell Biol 91: 116–122.
59. LeeS, LeeJW, LeeSK (2012) UTX, a Histone H3-Lysine 27 Demethylase, Acts as a Critical Switch to Activate the Cardiac Developmental Program. Dev Cell
60. HuangC, XiangY, WangY, LiX, XuL, et al. (2010) Dual-specificity histone demethylase KIAA1718 (KDM7A) regulates neural differentiation through FGF4. Cell Res 20: 154–165.
61. LoenarzC, GeW, ColemanML, RoseNR, CooperCD, et al. (2010) PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for an Nepsilon-dimethyl lysine demethylase. Hum Mol Genet 19: 217–222.
62. YuL, WangY, HuangS, WangJ, DengZ, et al. (2010) Structural insights into a novel histone demethylase PHF8. Cell Res 20: 166–173.
63. SengokuT, YokoyamaS (2011) Structural basis for histone H3 Lys 27 demethylation by UTX/KDM6A. Genes Dev 25: 2266–2277.
64. ChenZ, ZangJ, KapplerJ, HongX, CrawfordF, et al. (2007) Structural basis of the recognition of a methylated histone tail by JMJD2A. Proc Natl Acad Sci U S A 104: 10818–10823.
65. DealRB, HenikoffJG, HenikoffS (2010) Genome-wide kinetics of nucleosome turnover determined by metabolic labeling of histones. Science 328: 1161–1164.
66. HansenKH, BrackenAP, PasiniD, DietrichN, GehaniSS, et al. (2008) A model for transmission of the H3K27me3 epigenetic mark. Nat Cell Biol 10: 1291–1300.
67. PetrukS, SedkovY, JohnstonDM, HodgsonJW, BlackKL, et al. (2012) TrxG and PcG proteins but not methylated histones remain associated with DNA through replication. Cell 150: 922–933.
68. FrancisNJ, FollmerNE, SimonMD, AghiaG, ButlerJD (2009) Polycomb proteins remain bound to chromatin and DNA during DNA replication in vitro. Cell 137: 110–122.
69. InoueA, ZhangY (2011) Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos. Science 334: 194.
70. OhnoR, NakayamaM, NaruseC, OkashitaN, TakanoO, et al. (2013) A replication-dependent passive mechanism modulates DNA demethylation in mouse primordial germ cells. Development 140: 2892–903 doi: 10.1242/dev.093229
71. MillerSA, MohnSE, WeinmannAS (2010) Jmjd3 and UTX play a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression. Mol Cell 40: 594–605.
72. VandammeJ, LettierG, SidoliS, Di SchiaviE, Norregaard JensenO, et al. (2012) The C. elegans H3K27 demethylase UTX-1 is essential for normal development, independent of its enzymatic activity. PLoS Genet 8: e1002647.
73. GallardoT, ShirleyL, JohnGB, CastrillonDH (2007) Generation of a germ cell-specific mouse transgenic Cre line, Vasa-Cre. Genesis 45: 413–417.
74. RahlPB, LinCY, SeilaAC, FlynnRA, McCuineS, et al. (2010) c-Myc regulates transcriptional pause release. Cell 141: 432–445.
75. CalabreseJM, SunW, SongL, MugfordJW, WilliamsL, et al. (2012) Site-specific silencing of regulatory elements as a mechanism of X inactivation. Cell 151: 951–963.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2014 Číslo 8
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Meta-Analysis of Genome-Wide Association Studies in African Americans Provides Insights into the Genetic Architecture of Type 2 Diabetes
- KDM6 Demethylase Independent Loss of Histone H3 Lysine 27 Trimethylation during Early Embryonic Development
- The RNA Helicases AtMTR4 and HEN2 Target Specific Subsets of Nuclear Transcripts for Degradation by the Nuclear Exosome in
- EF-P Dependent Pauses Integrate Proximal and Distal Signals during Translation