#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Epigenetic Regulation of a Murine Retrotransposon by a Dual Histone Modification Mark


Large fractions of eukaryotic genomes contain repetitive sequences of which the vast majority is derived from transposable elements (TEs). In order to inactivate those potentially harmful elements, host organisms silence TEs via methylation of transposon DNA and packaging into chromatin associated with repressive histone marks. The contribution of individual histone modifications in this process is not completely resolved. Therefore, we aimed to define the role of reversible histone acetylation, a modification commonly associated with transcriptional activity, in transcriptional regulation of murine TEs. We surveyed histone acetylation patterns and expression levels of ten different murine TEs in mouse fibroblasts with altered histone acetylation levels, which was achieved via chemical HDAC inhibition with trichostatin A (TSA), or genetic inactivation of the major deacetylase HDAC1. We found that one LTR retrotransposon family encompassing virus-like 30S elements (VL30) showed significant histone H3 hyperacetylation and strong transcriptional activation in response to TSA treatment. Analysis of VL30 transcripts revealed that increased VL30 transcription is due to enhanced expression of a limited number of genomic elements, with one locus being particularly responsive to HDAC inhibition. Importantly, transcriptional induction of VL30 was entirely dependent on the activation of MAP kinase pathways, resulting in serine 10 phosphorylation at histone H3. Stimulation of MAP kinase cascades together with HDAC inhibition led to simultaneous phosphorylation and acetylation (phosphoacetylation) of histone H3 at the VL30 regulatory region. The presence of the phosphoacetylation mark at VL30 LTRs was linked with full transcriptional activation of the mobile element. Our data indicate that the activity of different TEs is controlled by distinct chromatin modifications. We show that activation of a specific mobile element is linked to a dual epigenetic mark and propose a model whereby phosphoacetylation of histone H3 is crucial for full transcriptional activation of VL30 elements.


Vyšlo v časopise: Epigenetic Regulation of a Murine Retrotransposon by a Dual Histone Modification Mark. PLoS Genet 6(4): e32767. doi:10.1371/journal.pgen.1000927
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1000927

Souhrn

Large fractions of eukaryotic genomes contain repetitive sequences of which the vast majority is derived from transposable elements (TEs). In order to inactivate those potentially harmful elements, host organisms silence TEs via methylation of transposon DNA and packaging into chromatin associated with repressive histone marks. The contribution of individual histone modifications in this process is not completely resolved. Therefore, we aimed to define the role of reversible histone acetylation, a modification commonly associated with transcriptional activity, in transcriptional regulation of murine TEs. We surveyed histone acetylation patterns and expression levels of ten different murine TEs in mouse fibroblasts with altered histone acetylation levels, which was achieved via chemical HDAC inhibition with trichostatin A (TSA), or genetic inactivation of the major deacetylase HDAC1. We found that one LTR retrotransposon family encompassing virus-like 30S elements (VL30) showed significant histone H3 hyperacetylation and strong transcriptional activation in response to TSA treatment. Analysis of VL30 transcripts revealed that increased VL30 transcription is due to enhanced expression of a limited number of genomic elements, with one locus being particularly responsive to HDAC inhibition. Importantly, transcriptional induction of VL30 was entirely dependent on the activation of MAP kinase pathways, resulting in serine 10 phosphorylation at histone H3. Stimulation of MAP kinase cascades together with HDAC inhibition led to simultaneous phosphorylation and acetylation (phosphoacetylation) of histone H3 at the VL30 regulatory region. The presence of the phosphoacetylation mark at VL30 LTRs was linked with full transcriptional activation of the mobile element. Our data indicate that the activity of different TEs is controlled by distinct chromatin modifications. We show that activation of a specific mobile element is linked to a dual epigenetic mark and propose a model whereby phosphoacetylation of histone H3 is crucial for full transcriptional activation of VL30 elements.


Zdroje

1. StrahlBD

AllisCD

2000 The language of covalent histone modifications. Nature 403 41 45

2. YangXJ

SetoE

2008 The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat Rev Mol Cell Biol 9 206 218

3. WangZ

ZangC

CuiK

SchonesDE

BarskiA

2009 Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes. Cell 138 1019 1031

4. MarksP

RifkindRA

RichonVM

BreslowR

MillerT

2001 Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer 1 194 202

5. ShankarS

SrivastavaRK

2008 Histone deacetylase inhibitors: mechanisms and clinical significance in cancer: HDAC inhibitor-induced apoptosis. Adv Exp Med Biol 615 261 298

6. BrunmeirR

LaggerS

SeiserC

2009 Histone deacetylase HDAC1/HDAC2-controlled embryonic development and cell differentiation. Int J Dev Biol 53 275 289

7. IkegamiK

OhganeJ

TanakaS

YagiS

ShiotaK

2009 Interplay between DNA methylation, histone modification and chromatin remodeling in stem cells and during development. Int J Dev Biol 53 203 214

8. LanderES

LintonLM

BirrenB

NusbaumC

ZodyMC

2001 Initial sequencing and analysis of the human genome. Nature 409 860 921

9. WaterstonRH

Lindblad-TohK

BirneyE

RogersJ

AbrilJF

2002 Initial sequencing and comparative analysis of the mouse genome. Nature 420 520 562

10. PrakET

KazazianHHJr

2000 Mobile elements and the human genome. Nat Rev Genet 1 134 144

11. GoodierJL

KazazianHHJr

2008 Retrotransposons revisited: the restraint and rehabilitation of parasites. Cell 135 23 35

12. MaksakovaIA

RomanishMT

GagnierL

DunnCA

van de LagemaatLN

2006 Retroviral elements and their hosts: insertional mutagenesis in the mouse germ line. PLoS Genet 2 e2 doi:10.1371/journal.pgen.0020002

13. MaksakovaIA

MagerDL

ReissD

2008 Keeping active endogenous retroviral-like elements in check: the epigenetic perspective. Cell Mol Life Sci 65 3329 3347

14. GoffSP

2004 Retrovirus restriction factors. Mol Cell 16 849 859

15. MartensJH

O'SullivanRJ

BraunschweigU

OpravilS

RadolfM

2005 The profile of repeat-associated histone lysine methylation states in the mouse epigenome. Embo J 24 800 812

16. MatsuiT

LeungD

MiyashitaH

MaksakovaI

MiyachiH

2010 Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature advance online publication doi:10.1038/nature08858

17. SlotkinRK

MartienssenR

2007 Transposable elements and the epigenetic regulation of the genome. Nat Rev Genet 8 272 285

18. CamHP

ChenES

GrewalSI

2009 Transcriptional scaffolds for heterochromatin assembly. Cell 136 610 614

19. MaloneCD

HannonGJ

2009 Small RNAs as guardians of the genome. Cell 136 656 668

20. ObbardDJ

FinneganDJ

2008 RNA interference: endogenous siRNAs derived from transposable elements. Curr Biol 18 R561 563

21. MatzkeM

KannoT

DaxingerL

HuettelB

MatzkeAJ

2009 RNA-mediated chromatin-based silencing in plants. Curr Opin Cell Biol 21 367 376

22. McClintockB

1984 The significance of responses of the genome to challenge. Science 226 792 801

23. CapyP

GasperiG

BiemontC

BazinC

2000 Stress and transposable elements: co-evolution or useful parasites? Heredity 85 (Pt 2) 101 106

24. PanningB

SmileyJR

1993 Activation of RNA polymerase III transcription of human Alu repetitive elements by adenovirus type 5: requirement for the E1b 58-kilodalton protein and the products of E4 open reading frames 3 and 6. Mol Cell Biol 13 3231 3244

25. LiuWM

ChuWM

ChoudaryPV

SchmidCW

1995 Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts. Nucleic Acids Res 23 1758 1765

26. StribinskisV

RamosKS

2006 Activation of human long interspersed nuclear element 1 retrotransposition by benzo(a)pyrene, an ubiquitous environmental carcinogen. Cancer Res 66 2616 2620

27. FrenchNS

NortonJD

1997 Structure and functional properties of mouse VL30 retrotransposons. Biochim Biophys Acta 1352 33 47

28. JanuchowskiR

DabrowskiM

OforiH

JagodzinskiPP

2007 Trichostatin A down-regulate DNA methyltransferase 1 in Jurkat T cells. Cancer Lett 246 313 317

29. YouJS

KangJK

LeeEK

LeeJC

LeeSH

2008 Histone deacetylase inhibitor apicidin downregulates DNA methyltransferase 1 expression and induces repressive histone modifications via recruitment of corepressor complex to promoter region in human cervix cancer cells. Oncogene 27 1376 1386

30. SchermellehL

SpadaF

EaswaranHP

ZolghadrK

MargotJB

2005 Trapped in action: direct visualization of DNA methyltransferase activity in living cells. Nat Methods 2 751 756

31. GhoshalK

DattaJ

MajumderS

BaiS

KutayH

2005 5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal. Mol Cell Biol 25 4727 4741

32. GonzalgoML

JonesPA

1997 Rapid quantitation of methylation differences at specific sites using methylation-sensitive single nucleotide primer extension (Ms-SNuPE). Nucleic Acids Res 25 2529 2531

33. LaneN

DeanW

ErhardtS

HajkovaP

SuraniA

2003 Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 35 88 93

34. LaggerG

O'CarrollD

RemboldM

KhierH

TischlerJ

2002 Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression. Embo J 21 2672 2681

35. PeastonAE

EvsikovAV

GraberJH

de VriesWN

HolbrookAE

2004 Retrotransposons regulate host genes in mouse oocytes and preimplantation embryos. Dev Cell 7 597 606

36. StockingC

KozakCA

2008 Murine endogenous retroviruses. Cell Mol Life Sci 65 3383 3398

37. DavisCM

ConstantinidesPG

van der RietF

van SchalkwykL

GeversW

1989 Activation and demethylation of the intracisternal A particle genes by 5-azacytidine. Cell Differ Dev 27 83 93

38. WalshCP

ChailletJR

BestorTH

1998 Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat Genet 20 116 117

39. TzavarasT

EftaxiaS

TavoulariS

HatziP

AngelidisC

2003 Factors influencing the expression of endogenous reverse transcriptases and viral-like 30 elements in mouse NIH3T3 cells. Int J Oncol 23 1237 1243

40. MaksakovaIA

MagerDL

2005 Transcriptional regulation of early transposon elements, an active family of mouse long terminal repeat retrotransposons. J Virol 79 13865 13874

41. ScholesDT

BanerjeeM

BowenB

CurcioMJ

2001 Multiple regulators of Ty1 transposition in Saccharomyces cerevisiae have conserved roles in genome maintenance. Genetics 159 1449 1465

42. GriffithJL

ColemanLE

RaymondAS

GoodsonSG

PittardWS

2003 Functional genomics reveals relationships between the retrovirus-like Ty1 element and its host Saccharomyces cerevisiae. Genetics 164 867 879

43. AyeM

IrwinB

Beliakova-BethellN

ChenE

GarrusJ

2004 Host factors that affect Ty3 retrotransposition in Saccharomyces cerevisiae. Genetics 168 1159 1176

44. IrwinB

AyeM

BaldiP

Beliakova-BethellN

ChengH

2005 Retroviruses and yeast retrotransposons use overlapping sets of host genes. Genome Res 15 641 654

45. NyswanerKM

CheckleyMA

YiM

StephensRM

GarfinkelDJ

2008 Chromatin-associated genes protect the yeast genome from Ty1 insertional mutagenesis. Genetics 178 197 214

46. HeidmannO

HeidmannT

1991 Retrotransposition of a mouse IAP sequence tagged with an indicator gene. Cell 64 159 170

47. MoranJV

HolmesSE

NaasTP

DeBerardinisRJ

BoekeJD

1996 High frequency retrotransposition in cultured mammalian cells. Cell 87 917 927

48. EsnaultC

HeidmannO

DelebecqueF

DewannieuxM

RibetD

2005 APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses. Nature 433 430 433

49. MietzJA

FewellJW

KuffEL

1992 Selective activation of a discrete family of endogenous proviral elements in normal BALB/c lymphocytes. Mol Cell Biol 12 220 228

50. NilssonM

BohmS

1994 Inducible and cell type-specific expression of VL30 U3 subgroups correlate with their enhancer design. J Virol 68 276 288

51. NoutsopoulosD

MarkopoulosG

KoliouM

DovaL

VartholomatosG

2007 Vanadium induces VL30 retrotransposition at an unusually high level: a possible carcinogenesis mechanism. J Mol Biol 374 80 90

52. MahadevanLC

WillisAC

BarrattMJ

1991 Rapid histone H3 phosphorylation in response to growth factors, phorbol esters, okadaic acid, and protein synthesis inhibitors. Cell 65 775 783

53. ThomsonS

ClaytonAL

HazzalinCA

RoseS

BarrattMJ

1999 The nucleosomal response associated with immediate-early gene induction is mediated via alternative MAP kinase cascades: MSK1 as a potential histone H3/HMG-14 kinase. Embo J 18 4779 4793

54. CheungP

TannerKG

CheungWL

Sassone-CorsiP

DenuJM

2000 Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation. Mol Cell 5 905 915

55. ClaytonAL

RoseS

BarrattMJ

MahadevanLC

2000 Phosphoacetylation of histone H3 on c-fos- and c-jun-associated nucleosomes upon gene activation. Embo J 19 3714 3726

56. LiJ

GorospeM

HutterD

BarnesJ

KeyseSM

2001 Transcriptional induction of MKP-1 in response to stress is associated with histone H3 phosphorylation-acetylation. Mol Cell Biol 21 8213 8224

57. HauserC

SchuettengruberB

BartlS

LaggerG

SeiserC

2002 Activation of the mouse histone deacetylase 1 gene by cooperative histone phosphorylation and acetylation. Mol Cell Biol 22 7820 7830

58. WinterS

SimboeckE

FischleW

ZupkovitzG

DohnalI

2008 14-3-3 proteins recognize a histone code at histone H3 and are required for transcriptional activation. Embo J 27 88 99

59. KurdistaniSK

TavazoieS

GrunsteinM

2004 Mapping global histone acetylation patterns to gene expression. Cell 117 721 733

60. KochCM

AndrewsRM

FlicekP

DillonSC

KaraozU

2007 The landscape of histone modifications across 1% of the human genome in five human cell lines. Genome Res 17 691 707

61. FischerJJ

ToedlingJ

KruegerT

SchuelerM

HuberW

2008 Combinatorial effects of four histone modifications in transcription and differentiation. Genomics 91 41 51

62. GlozakMA

SetoE

2007 Histone deacetylases and cancer. Oncogene 26 5420 5432

63. KalkhovenE

2004 CBP and p300: HATs for different occasions. Biochem Pharmacol 68 1145 1155

64. HeG

MargolisDM

2002 Counterregulation of chromatin deacetylation and histone deacetylase occupancy at the integrated promoter of human immunodeficiency virus type 1 (HIV-1) by the HIV-1 repressor YY1 and HIV-1 activator Tat. Mol Cell Biol 22 2965 2973

65. LusicM

MarcelloA

CeresetoA

GiaccaM

2003 Regulation of HIV-1 gene expression by histone acetylation and factor recruitment at the LTR promoter. Embo J 22 6550 6561

66. GarrisonBS

YantSR

MikkelsenJG

KayMA

2007 Postintegrative gene silencing within the Sleeping Beauty transposition system. Mol Cell Biol 27 8824 8833

67. BranciforteD

MartinSL

1994 Developmental and cell type specificity of LINE-1 expression in mouse testis: implications for transposition. Mol Cell Biol 14 2584 2592

68. DupressoirA

HeidmannT

1996 Germ line-specific expression of intracisternal A-particle retrotransposons in transgenic mice. Mol Cell Biol 16 4495 4503

69. SeifarthW

FrankO

ZeilfelderU

SpiessB

GreenwoodAD

2005 Comprehensive analysis of human endogenous retrovirus transcriptional activity in human tissues with a retrovirus-specific microarray. J Virol 79 341 352

70. IshiharaH

TanakaI

WanH

NojimaK

YoshidaK

2004 Retrotransposition of limited deletion type of intracisternal A-particle elements in the myeloid leukemia Clls of C3H/He mice. J Radiat Res (Tokyo) 45 25 32

71. CostainWJ

RasquinhaI

GraberT

LuebbertC

PrestonE

2006 Cerebral ischemia induces neuronal expression of novel VL30 mouse retrotransposons bound to polyribosomes. Brain Res 1094 24 37

72. RauchTA

ZhongX

WuX

WangM

KernstineKH

2008 High-resolution mapping of DNA hypermethylation and hypomethylation in lung cancer. Proc Natl Acad Sci U S A 105 252 257

73. WilsonAS

PowerBE

MolloyPL

2007 DNA hypomethylation and human diseases. Biochim Biophys Acta 1775 138 162

74. ColmegnaI

GarryRF

2006 Role of endogenous retroviruses in autoimmune diseases. Infect Dis Clin North Am 20 913 929

75. SongX

SuiA

GarenA

2004 Binding of mouse VL30 retrotransposon RNA to PSF protein induces genes repressed by PSF: effects on steroidogenesis and oncogenesis. Proc Natl Acad Sci U S A 101 621 626

76. SongX

SunY

GarenA

2005 Roles of PSF protein and VL30 RNA in reversible gene regulation. Proc Natl Acad Sci U S A 102 12189 12193

77. MillerWJ

McDonaldJF

NouaudD

AnxolabehereD

1999 Molecular domestication–more than a sporadic episode in evolution. Genetica 107 197 207

78. EspinoPS

LiL

HeS

YuJ

DavieJR

2006 Chromatin modification of the trefoil factor 1 gene in human breast cancer cells by the Ras/mitogen-activated protein kinase pathway. Cancer Res 66 4610 4616

79. WiechNL

FisherJF

HelquistP

WiestO

2009 Inhibition of histone deacetylases: a pharmacological approach to the treatment of non-cancer disorders. Curr Top Med Chem 9 257 271

80. RotiliD

SimonettiG

SavarinoA

PalamaraAT

MigliaccioAR

2009 Non-cancer uses of histone deacetylase inhibitors: effects on infectious diseases and beta-hemoglobinopathies. Curr Top Med Chem 9 272 291

81. LiL

FengT

LianY

ZhangG

GarenA

2009 Role of human noncoding RNAs in the control of tumorigenesis. Proc Natl Acad Sci U S A

82. YamaguchiT

CubizollesF

ZhangY

ReichertN

KohlerH

Histone deacetylases 1 and 2 act in concert to promote the G1-to-S progression. Genes Dev 24 455 469

83. TodaroGJ

GreenH

1963 Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J Cell Biol 17 299 313

84. PuschendorfM

SteinP

OakeleyEJ

SchultzRM

PetersAH

2006 Abundant transcripts from retrotransposons are unstable in fully grown mouse oocytes. Biochem Biophys Res Commun 347 36 43

85. CarterAT

NortonJD

AveryRJ

1983 A novel approach to cloning transcriptionally active retrovirus-like genetic elements from mouse cells. Nucleic Acids Res 11 6243 6254

86. EatonL

NortonJD

1990 Independent regulation of mouse VL30 retrotransposon expression in response to serum and oncogenic cell transformation. Nucleic Acids Res 18 2069 2077

87. HodgsonCP

ElderPK

OnoT

FosterDN

GetzMJ

1983 Structure and expression of mouse VL30 genes. Mol Cell Biol 3 2221 2231

88. WickerT

SabotF

Hua-VanA

BennetzenJL

CapyP

2007 A unified classification system for eukaryotic transposable elements. Nat Rev Genet 8 973 982

89. SmitAF

1993 Identification of a new, abundant superfamily of mammalian LTR-transposons. Nucleic Acids Res 21 1863 1872

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2010 Číslo 4
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#