Histone Methyltransferase DOT1L Drives Recovery of Gene Expression after a Genotoxic Attack

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UV-induced DNA damage causes repression of RNA synthesis. Following the removal of DNA lesions, transcription recovery operates through a process that is not understood yet. Here we show that knocking-out of the histone methyltransferase DOT1L in mouse embryonic fibroblasts (MEF^DOT1L) leads to a UV hypersensitivity coupled to a deficient recovery of transcription initiation after UV irradiation. However, DOT1L is not implicated in the removal of the UV-induced DNA damage by the nucleotide excision repair pathway. Using FRAP and ChIP experiments we established that DOT1L promotes the formation of the pre-initiation complex on the promoters of UV-repressed genes and the appearance of transcriptionally active chromatin marks. Treatment with Trichostatin A, relaxing chromatin, recovers both transcription initiation and UV-survival. Our data suggest that DOT1L secures an open chromatin structure in order to reactivate RNA Pol II transcription initiation after a genotoxic attack.

Vyšlo v časopise: Histone Methyltransferase DOT1L Drives Recovery of Gene Expression after a Genotoxic Attack. PLoS Genet 9(7): e32767. doi:10.1371/journal.pgen.1003611
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003611

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Zdroje

1. FriedbergEC, AguileraA, GellertM, HanawaltPC, HaysJB, et al. (2006) DNA repair: from molecular mechanism to human disease. DNA Repair (Amst) 5: 986–996.

2. CitterioE, Van Den BoomV, SchnitzlerG, KanaarR, BonteE, et al. (2000) ATP-dependent chromatin remodeling by the Cockayne syndrome B DNA repair-transcription-coupling factor. Mol Cell Biol 20: 7643–7653.

3. Proietti-De-SantisL, DraneP, EglyJM (2006) Cockayne syndrome B protein regulates the transcriptional program after UV irradiation. Embo J 25: 1915–1923.

4. HanawaltPC (2002) Subpathways of nucleotide excision repair and their regulation. Oncogene 21: 8949–8956.

5. FousteriM, MullendersLH (2008) Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects. Cell Res 18: 73–84.

6. ShilatifardA (2006) Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu Rev Biochem 75: 243–269.

7. KouzaridesT (2007) Chromatin modifications and their function. Cell 128: 693–705.

8. CamposEI, ReinbergD (2009) Histones: annotating chromatin. Annu Rev Genet 43: 559–599.

9. FengQ, WangH, NgHH, Erdjument-BromageH, TempstP, et al. (2002) Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain. Curr Biol 12: 1052–1058.

10. LacosteN, UtleyRT, HunterJM, PoirierGG, CoteJ (2002) Disruptor of telomeric silencing-1 is a chromatin-specific histone H3 methyltransferase. J Biol Chem 277: 30421–30424.

11. van LeeuwenF, GafkenPR, GottschlingDE (2002) Dot1p modulates silencing in yeast by methylation of the nucleosome core. Cell 109: 745–756.

12. LugerK, MaderAW, RichmondRK, SargentDF, RichmondTJ (1997) Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389: 251–260.

13. MinJ, FengQ, LiZ, ZhangY, XuRM (2003) Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase. Cell 112: 711–723.

14. SawadaK, YangZ, HortonJR, CollinsRE, ZhangX, et al. (2004) Structure of the conserved core of the yeast Dot1p, a nucleosomal histone H3 lysine 79 methyltransferase. J Biol Chem 279: 43296–43306.

15. NguyenAT, ZhangY (2011) The diverse functions of Dot1 and H3K79 methylation. Genes Dev 25: 1345–1358.

16. OnderTT, KaraN, CherryA, SinhaAU, ZhuN, et al. (2012) Chromatin-modifying enzymes as modulators of reprogramming. Nature 483: 598–602.

17. OkadaY, FengQ, LinY, JiangQ, LiY, et al. (2005) hDOT1L links histone methylation to leukemogenesis. Cell 121: 167–178.

18. HuyenY, ZgheibO, DitullioRAJr, GorgoulisVG, ZacharatosP, et al. (2004) Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 432: 406–411.

19. GiannattasioM, LazzaroF, PlevaniP, Muzi-FalconiM (2005) The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1. J Biol Chem 280: 9879–9886.

20. WysockiR, JavaheriA, AllardS, ShaF, CoteJ, et al. (2005) Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9. Mol Cell Biol 25: 8430–8443.

21. TohGW, O'ShaughnessyAM, JimenoS, DobbieIM, GrenonM, et al. (2006) Histone H2A phosphorylation and H3 methylation are required for a novel Rad9 DSB repair function following checkpoint activation. DNA Repair (Amst) 5: 693–703.

22. BostelmanLJ, KellerAM, AlbrechtAM, AratA, ThompsonJS (2007) Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae. DNA Repair (Amst) 6: 383–395.

23. StegerDJ, LefterovaMI, YingL, StonestromAJ, SchuppM, et al. (2008) DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells. Mol Cell Biol 28: 2825–2839.

24. ShiomiN, MoriM, KitoS, HaradaYN, TanakaK, et al. (2005) Severe growth retardation and short life span of double-mutant mice lacking Xpa and exon 15 of Xpg. DNA Repair (Amst) 4: 351–357.

25. StefaniniM, GilianiS, NardoT, MarinoniS, NazzaroV, et al. (1992) DNA repair investigations in nine Italian patients affected by trichothiodystrophy. Mutat Res 273: 119–125.

26. TakebayashiY, PourquierP, ZimonjicDB, NakayamaK, EmmertS, et al. (2001) Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair. Nat Med 7: 961–966.

27. CarreauM, EvenoE, QuillietX, Chevalier-LagenteO, BenoitA, et al. (1995) Development of a new easy complementation assay for DNA repair deficient human syndromes using cloned repair genes. Carcinogenesis 16: 1003–1009.

28. SinghJ, PadgettRA (2009) Rates of in situ transcription and splicing in large human genes. Nat Struct Mol Biol 16: 1128–1133.

29. CoinF, OksenychV, MocquetV, GrohS, BlattnerC, et al. (2008) Nucleotide excision repair driven by the dissociation of CAK from TFIIH. Mol Cell 31: 9–20.

30. TatumD, LiS (2011) Evidence that the histone methyltransferase Dot1 mediates global genomic repair by methylating histone H3 on lysine 79. J Biol Chem 286: 17530–17535.

31. AndressooJO, MitchellJR, de WitJ, HoogstratenD, VolkerM, et al. (2006) An Xpd mouse model for the combined xeroderma pigmentosum/Cockayne syndrome exhibiting both cancer predisposition and segmental progeria. Cancer Cell 10: 121–132.

32. van OosterwijkMF, VersteegA, FilonR, van ZeelandAA, MullendersLH (1996) The sensitivity of Cockayne's syndrome cells to DNA-damaging agents is not due to defective transcription-coupled repair of active genes. Mol Cell Biol 16: 4436–4444.

33. NgHH, CicconeDN, MorsheadKB, OettingerMA, StruhlK (2003) Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: a potential mechanism for position-effect variegation. Proc Natl Acad Sci U S A 100: 1820–1825.

34. NgHH, FengQ, WangH, Erdjument-BromageH, TempstP, et al. (2002) Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association. Genes Dev 16: 1518–1527.

35. JohnsonA, LiG, SikorskiTW, BuratowskiS, WoodcockCL, et al. (2009) Reconstitution of heterochromatin-dependent transcriptional gene silencing. Mol Cell 35: 769–781.

36. NguyenVT, GiannoniF, DuboisMF, SeoSJ, VigneronM, et al. (1996) In vivo degradation of RNA polymerase II largest subunit triggered by alpha-amanitin. Nucleic Acids Res 24: 2924–2929.

37. Giglia-MariG, MiquelC, TheilAF, MariPO, HoogstratenD, et al. (2006) Dynamic interaction of TTDA with TFIIH is stabilized by nucleotide excision repair in living cells. PLoS Biol 4: e156.

38. van der HorstGT, van SteegH, BergRJ, van GoolAJ, de WitJ, et al. (1997) Defective transcription-coupled repair in Cockayne syndrome B mice is associated with skin cancer predisposition. Cell 89: 425–435.

39. HaradaYN, ShiomiN, KoikeM, IkawaM, OkabeM, et al. (1999) Postnatal growth failure, short life span, and early onset of cellular senescence and subsequent immortalization in mice lacking the xeroderma pigmentosum group G gene. Mol Cell Biol 19: 2366–2372.