Interactions of Chromatin Context, Binding Site Sequence Content, and Sequence Evolution in Stress-Induced p53 Occupancy and Transactivation


It is well established that p53 binds DNA elements near p53 target genes to regulate the response to cellular stress. To assess factors influencing binding to response elements and subsequent gene expression, we have analyzed 2932 p53-occupied response elements (p53REs) in the context of genome-wide chromatin state, DNA accessibility and dynamics, and considered roles for binding-sequence specificity and evolutionary conservation. While p53 occupancy level shows little apparent direct relationship to gene expression change, after grouping expressed genes by their chromatin status at baseline, a relationship between occupancy of p53REs and gene expression change emerged. Analysis of p53RE sequences demonstrated that p53 occupancy was strongly correlated with sequence similarity to p53RE consensus, but surprisingly, was inversely correlated with nucleosome accessibility (DHS) and evolutionary conservation. These data revealed a systematic interaction between p53RE content and chromatin context that affects both quantitative p53 occupancy and the induced transactivation response to exposure. Moreover, this interaction appears to have been tuned via evolutionary events involving transposable elements, which strongly bind p53, but in only a few instances affect gene expression levels. Models of p53-regulated gene expression response that consider both chromatin state and sequence context may prove useful in guiding strategies for cancer prevention or therapy.


Vyšlo v časopise: Interactions of Chromatin Context, Binding Site Sequence Content, and Sequence Evolution in Stress-Induced p53 Occupancy and Transactivation. PLoS Genet 11(1): e32767. doi:10.1371/journal.pgen.1004885
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004885

Souhrn

It is well established that p53 binds DNA elements near p53 target genes to regulate the response to cellular stress. To assess factors influencing binding to response elements and subsequent gene expression, we have analyzed 2932 p53-occupied response elements (p53REs) in the context of genome-wide chromatin state, DNA accessibility and dynamics, and considered roles for binding-sequence specificity and evolutionary conservation. While p53 occupancy level shows little apparent direct relationship to gene expression change, after grouping expressed genes by their chromatin status at baseline, a relationship between occupancy of p53REs and gene expression change emerged. Analysis of p53RE sequences demonstrated that p53 occupancy was strongly correlated with sequence similarity to p53RE consensus, but surprisingly, was inversely correlated with nucleosome accessibility (DHS) and evolutionary conservation. These data revealed a systematic interaction between p53RE content and chromatin context that affects both quantitative p53 occupancy and the induced transactivation response to exposure. Moreover, this interaction appears to have been tuned via evolutionary events involving transposable elements, which strongly bind p53, but in only a few instances affect gene expression levels. Models of p53-regulated gene expression response that consider both chromatin state and sequence context may prove useful in guiding strategies for cancer prevention or therapy.


Zdroje

1. Gomez-LazaroM, Fernandez-GomezFJ, JordanJ (2004) p53: twenty five years understanding the mechanism of genome protection. Journal of physiology and biochemistry 60: 287–307.

2. SchetterAJ, HarrisCC (2012) Tumor suppressor p53 (TP53) at the crossroads of the exposome and the cancer genome. Proceedings of the National Academy of Sciences of the United States of America 109: 7955–7956.

3. RileyT, SontagE, ChenP, LevineA (2008) Transcriptional control of human p53-regulated genes. Nature reviews Molecular cell biology 9: 402–412.

4. ChanC, WangY, ChowPK, ChungAY, OoiLL, et al. (2013) Altered Binding Site Selection of p53 Transcription Cassettes by Hepatitis B Virus X Protein. Molecular and cellular biology 33: 485–497.

5. SmeenkL, van HeeringenSJ, KoeppelM, van DrielMA, BartelsSJ, et al. (2008) Characterization of genome-wide p53-binding sites upon stress response. Nucleic acids research 36: 3639–3654.

6. WeiCL, WuQ, VegaVB, ChiuKP, NgP, et al. (2006) A global map of p53 transcription-factor binding sites in the human genome. Cell 124: 207–219.

7. BotchevaK, McCorkleSR, McCombieWR, DunnJJ, AndersonCW (2011) Distinct p53 genomic binding patterns in normal and cancer-derived human cells. Cell cycle 10: 4237–4249.

8. NikulenkovF, SpinnlerC, LiH, TonelliC, ShiY, et al. (2012) Insights into p53 transcriptional function via genome-wide chromatin occupancy and gene expression analysis. Cell death and differentiation 19: 1992–2002.

9. MenendezD, NguyenTA, FreudenbergJM, MathewVJ, AndersonCW, et al. (2013) Diverse stresses dramatically alter genome-wide p53 binding and transactivation landscape in human cancer cells. Nucleic acids research 41: 7286–7301.

10. SmeenkL, van HeeringenSJ, KoeppelM, GilbertB, Janssen-MegensE, et al. (2011) Role of p53 serine 46 in p53 target gene regulation. PloS one 6: e17574.

11. AndrysikZ, KimJ, TanAC, EspinosaJM (2013) A genetic screen identifies TCF3/E2A and TRIAP1 as pathway-specific regulators of the cellular response to p53 activation. Cell reports 3: 1346–1354.

12. FreemanJA, EspinosaJM (2013) The impact of post-transcriptional regulation in the p53 network. Brief Funct Genomics 12: 46–57.

13. GomesNP, EspinosaJM (2010) Disparate chromatin landscapes and kinetics of inactivation impact differential regulation of p53 target genes. Cell cycle 9: 3428–3437.

14. Lidor NiliE, FieldY, LublingY, WidomJ, OrenM, et al. (2010) p53 binds preferentially to genomic regions with high DNA-encoded nucleosome occupancy. Genome research 20: 1361–1368.

15. MillauJF, BandeleOJ, PerronJ, BastienN, BouchardEF, et al. (2011) Formation of stress-specific p53 binding patterns is influenced by chromatin but not by modulation of p53 binding affinity to response elements. Nucleic acids research 39: 3053–3063.

16. BandeleOJ, WangX, CampbellMR, PittmanGS, BellDA (2011) Human single-nucleotide polymorphisms alter p53 sequence-specific binding at gene regulatory elements. Nucleic acids research 39: 178–189.

17. JordanJJ, MenendezD, IngaA, NoureddineM, BellDA, et al. (2008) Noncanonical DNA motifs as transactivation targets by wild type and mutant p53. PLoS genetics 4: e1000104.

18. TomsoDJ, IngaA, MenendezD, PittmanGS, CampbellMR, et al. (2005) Functionally distinct polymorphic sequences in the human genome that are targets for p53 transactivation. Proceedings of the National Academy of Sciences of the United States of America 102: 6431–6436.

19. WangB, XiaoZ, RenEC (2009) Redefining the p53 response element. Proceedings of the National Academy of Sciences of the United States of America 106: 14373–14378.

20. VeprintsevDB, FershtAR (2008) Algorithm for prediction of tumour suppressor p53 affinity for binding sites in DNA. Nucleic acids research 36: 1589–1598.

21. WangT, ZengJ, LoweCB, SellersRG, SalamaSR, et al. (2007) Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53. Proceedings of the National Academy of Sciences of the United States of America 104: 18613–18618.

22. CuiF, SirotinMV, ZhurkinVB (2011) Impact of Alu repeats on the evolution of human p53 binding sites. Biology direct 6: 2.

23. ZemojtelT, KielbasaSM, ArndtPF, BehrensS, BourqueG, et al. (2011) CpG deamination creates transcription factor-binding sites with high efficiency. Genome biology and evolution 3: 1304–1311.

24. HarrisCR, DewanA, ZupnickA, NormartR, GabrielA, et al. (2009) p53 responsive elements in human retrotransposons. Oncogene 28: 3857–3865.

25. SchmidtD, SchwaliePC, WilsonMD, BallesterB, GoncalvesA, et al. (2012) Waves of retrotransposon expansion remodel genome organization and CTCF binding in multiple mammalian lineages. Cell 148: 335–348.

26. JohnS, SaboPJ, ThurmanRE, SungMH, BiddieSC, et al. (2011) Chromatin accessibility pre-determines glucocorticoid receptor binding patterns. Nature genetics 43: 264–268.

27. Guertin MJ, Lis JT (2010) Chromatin landscape dictates HSF binding to target DNA elements. PLoS genetics 6.

28. ThurmanRE, RynesE, HumbertR, VierstraJ, MauranoMT, et al. (2012) The accessible chromatin landscape of the human genome. Nature 489: 75–82.

29. HonGC, HawkinsRD, RenB (2009) Predictive chromatin signatures in the mammalian genome. Human molecular genetics 18: R195–201.

30. SmirnovDA, MorleyM, ShinE, SpielmanRS, CheungVG (2009) Genetic analysis of radiation-induced changes in human gene expression. Nature 459: 587–U120.

31. NoureddineMA, MenendezD, CampbellMR, BandeleOJ, HorvathMM, et al. (2009) Probing the functional impact of sequence variation on p53-DNA interactions using a novel microsphere assay for protein-DNA binding with human cell extracts. PLoS genetics 5: e1000462.

32. DunhamI, KundajeA, AldredSF, CollinsPJ, DavisCA, et al. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57–74.

33. ErnstJ, KheradpourP, MikkelsenTS, ShoreshN, WardLD, et al. (2011) Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473: 43–49.

34. RamO, GorenA, AmitI, ShoreshN, YosefN, et al. (2011) Combinatorial patterning of chromatin regulators uncovered by genome-wide location analysis in human cells. Cell 147: 1628–1639.

35. RoblesAI, WangXW, HarrisCC (1999) Drug-induced apoptosis is delayed and reduced in XPD lymphoblastoid cell lines: possible role of TFIIH in p53-mediated apoptotic cell death. Oncogene 18: 4681–4688.

36. ValouevA, JohnsonDS, SundquistA, MedinaC, AntonE, et al. (2008) Genome-wide analysis of transcription factor binding sites based on ChIP-Seq data. Nature Methods 5: 829–834.

37. ShakedH, ShiffI, Kott-GutkowskiM, SiegfriedZ, HauptY, et al. (2008) Chromatin immunoprecipitation-on-chip reveals stress-dependent p53 occupancy in primary normal cells but not in established cell lines. Cancer research 68: 9671–9677.

38. HoffmanMM, ErnstJ, WilderSP, KundajeA, HarrisRS, et al. (2013) Integrative annotation of chromatin elements from ENCODE data. Nucleic acids research 41: 827–841.

39. Guertin MJ, Lis JT (2012) Mechanisms by which transcription factors gain access to target sequence elements in chromatin. Current opinion in genetics & development.

40. Bailey TL, Elkan C (1994) Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Menlo Park, California: AAAI Press.

41. Jordan JJ, Menendez D, Inga A, Nourredine M, Bell D, et al.. (2008) Noncanonical DNA Motifs as Transactivation Targets by Wild Type and Mutant p53. PLoS genetics 4.

42. VernotB, StergachisAB, MauranoMT, VierstraJ, NephS, et al. (2012) Personal and population genomics of human regulatory variation. Genome research 22: 1689–1697.

43. NephS, VierstraJ, StergachisAB, ReynoldsAP, HaugenE, et al. (2012) An expansive human regulatory lexicon encoded in transcription factor footprints. Nature 489: 83–90.

44. GbadegesinMA (2012) Transposable elements in the genomes: parasites, junks or drivers of evolution? African journal of medicine and medical sciences 41 Suppl: 13–25.

45. HorvathMM, WangX, ResnickMA, BellDA (2007) Divergent evolution of human p53 binding sites: cell cycle versus apoptosis. PLoS genetics 3: e127.

46. GiordanoJ, GeY, GelfandY, AbrusanG, BensonG, et al. (2007) Evolutionary history of mammalian transposons determined by genome-wide defragmentation. PLoS computational biology 3: e137.

47. PollardKS, HubiszMJ, RosenbloomKR, SiepelA (2010) Detection of nonneutral substitution rates on mammalian phylogenies. Genome research 20: 110–121.

48. JenKY, CheungVG (2005) Identification of novel p53 target genes in ionizing radiation response. Cancer research 65: 7666–7673.

49. GuentherMG, LevineSS, BoyerLA, JaenischR, YoungRA (2007) A chromatin landmark and transcription initiation at most promoters in human cells. Cell 130: 77–88.

50. OzsolakF, SongJS, LiuXS, FisherDE (2007) High-throughput mapping of the chromatin structure of human promoters. Nature biotechnology 25: 244–248.

51. GomesNP, EspinosaJM (2010) Gene-specific repression of the p53 target gene PUMA via intragenic CTCF-Cohesin binding. Genes & development 24: 1022–1034.

52. AkdemirKC, JainAK, AlltonK, AronowB, XuX, et al. (2014) Genome-wide profiling reveals stimulus-specific functions of p53 during differentiation and DNA damage of human embryonic stem cells. Nucleic Acids Res 42: 205–223.

53. DunhamI, KundajeA, AldredSF, CollinsPJ, DavisCA, et al. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57–74.

54. ErnstJ, PlastererHL, SimonI, Bar-JosephZ (2010) Integrating multiple evidence sources to predict transcription factor binding in the human genome. Genome research 20: 526–536.

55. Pique-RegiR, DegnerJF, PaiAA, GaffneyDJ, GiladY, et al. (2011) Accurate inference of transcription factor binding from DNA sequence and chromatin accessibility data. Genome research 21: 447–455.

56. LiM, HeY, DuboisW, WuX, ShiJ, et al. (2012) Distinct regulatory mechanisms and functions for p53-activated and p53-repressed DNA damage response genes in embryonic stem cells. Molecular cell 46: 30–42.

57. RobertsonAG, BilenkyM, TamA, ZhaoY, ZengT, et al. (2008) Genome-wide relationship between histone H3 lysine 4 mono- and tri-methylation and transcription factor binding. Genome research 18: 1906–1917.

58. Zeron-MedinaJ, WangX, RepapiE, CampbellMR, SuD, et al. (2013) A Polymorphic p53 Response Element in KIT Ligand Influences Cancer Risk and Has Undergone Natural Selection. Cell 155: 410–422.

59. LeonovaKI, BrodskyL, LipchickB, PalM, NovototskayaL, et al. (2013) p53 cooperates with DNA methylation and a suicidal interferon response to maintain epigenetic silencing of repeats and noncoding RNAs. Proceedings of the National Academy of Sciences of the United States of America 110: E89–98.

60. MicaleL, LoviglioMN, ManzoniM, FuscoC, AugelloB, et al. (2012) A fish-specific transposable element shapes the repertoire of p53 target genes in zebrafish. PloS one 7: e46642.

61. HudaA, Marino-RamirezL, JordanIK (2010) Epigenetic histone modifications of human transposable elements: genome defense versus exaptation. Mobile DNA 1: 2.

62. SongL, ZhangZ, GrasfederLL, BoyleAP, GiresiPG, et al. (2011) Open chromatin defined by DNaseI and FAIRE identifies regulatory elements that shape cell-type identity. Genome research 21: 1757–1767.

63. WassermanWW, SandelinA (2004) Applied bioinformatics for the identification of regulatory elements. Nature reviews Genetics 5: 276–287.

64. WangX, TomsoDJ, ChorleyBN, ChoHY, CheungVG, et al. (2007) Identification of polymorphic antioxidant response elements in the human genome. Human molecular genetics 16: 1188–1200.

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Genetika Reprodukčná medicína

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