#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The Sequence-Specific Transcription Factor c-Jun Targets Cockayne Syndrome Protein B to Regulate Transcription and Chromatin Structure


Cockayne syndrome is a devastating inherited disease, in which patients appear to age prematurely, have sun sensitivity and suffer from profound neurological and developmental defects. Mutations in the CSB gene account for the majority of Cockayne syndrome cases. CSB is an ATP-dependent chromatin remodeler, and these proteins can use energy from ATP-hydrolysis to alter contacts between DNA and histones of a nucleosome, the basic units of chromatin structure. CSB functions in DNA repair, but accumulating evidence reveals that CSB also functions in transcription regulation. Here, we determined the genomic localization of CSB to identify its gene targets and found that CSB occupancy displays high correlation to regions with epigenetic features of promoters and enhancers. Furthermore, CSB is enriched at genomic regions containing the binding site for the c-Jun transcription factor, and we found that these two proteins interact, uncovering a new targeting mechanism for CSB. We also demonstrate that CSB can influence gene expression in the vicinity of its binding sites and alter local chromatin structure. Together, this study supports the hypothesis that defects in the regulation of gene expression and chromatin structure by CSB might contribute to the diverse clinical features of Cockayne syndrome.


Vyšlo v časopise: The Sequence-Specific Transcription Factor c-Jun Targets Cockayne Syndrome Protein B to Regulate Transcription and Chromatin Structure. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004284
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004284

Souhrn

Cockayne syndrome is a devastating inherited disease, in which patients appear to age prematurely, have sun sensitivity and suffer from profound neurological and developmental defects. Mutations in the CSB gene account for the majority of Cockayne syndrome cases. CSB is an ATP-dependent chromatin remodeler, and these proteins can use energy from ATP-hydrolysis to alter contacts between DNA and histones of a nucleosome, the basic units of chromatin structure. CSB functions in DNA repair, but accumulating evidence reveals that CSB also functions in transcription regulation. Here, we determined the genomic localization of CSB to identify its gene targets and found that CSB occupancy displays high correlation to regions with epigenetic features of promoters and enhancers. Furthermore, CSB is enriched at genomic regions containing the binding site for the c-Jun transcription factor, and we found that these two proteins interact, uncovering a new targeting mechanism for CSB. We also demonstrate that CSB can influence gene expression in the vicinity of its binding sites and alter local chromatin structure. Together, this study supports the hypothesis that defects in the regulation of gene expression and chromatin structure by CSB might contribute to the diverse clinical features of Cockayne syndrome.


Zdroje

1. NanceMA, BerrySA (1992) Cockayne syndrome: review of 140 cases. Am J Med Genet 42: 68–84.

2. LakeRJ, FanHY (2013) Structure, function and regulation of CSB: a multi-talented gymnast. Mech Ageing Dev 134: 202–211.

3. ClapierCR, CairnsBR (2009) The biology of chromatin remodeling complexes. Annu Rev Biochem 78: 273–304.

4. NarlikarGJ, FanHY, KingstonRE (2002) Cooperation between complexes that regulate chromatin structure and transcription. Cell 108: 475–487.

5. TorigoeSE, PatelA, KhuongMT, BowmanGD, KadonagaJT (2013) ATP-dependent chromatin assembly is functionally distinct from chromatin remodeling. eLife 2: e00863.

6. PhelanML, SifS, NarlikarGJ, KingstonRE (1999) Reconstitution of a core chromatin remodeling complex from SWI/SNF subunits. Mol Cell 3: 247–253.

7. WuJI, LessardJ, OlaveIA, QiuZ, GhoshA, et al. (2007) Regulation of dendritic development by neuron-specific chromatin remodeling complexes. Neuron 56: 94–108.

8. ChoI, TsaiPF, LakeRJ, BasheerA, FanHY (2013) ATP-Dependent Chromatin Remodeling by Cockayne Syndrome Protein B and NAP1-Like Histone Chaperones Is Required for Efficient Transcription-Coupled DNA Repair. PLoS Genet 9: e1003407.

9. AubleDT, HansenKE, MuellerCG, LaneWS, ThornerJ, et al. (1994) Mot1, a global repressor of RNA polymerase II transcription, inhibits TBP binding to DNA by an ATP-dependent mechanism. Genes Dev 8: 1920–1934.

10. SelbyCP, SancarA (1997) Human transcription-repair coupling factor CSB/ERCC6 is a DNA-stimulated ATPase but is not a helicase and does not disrupt the ternary transcription complex of stalled RNA polymerase II. J Biol Chem 272: 1885–1890.

11. CitterioE, RademakersS, van der HorstGT, van GoolAJ, HoeijmakersJH, et al. (1998) Biochemical and biological characterization of wild-type and ATPase-deficient Cockayne syndrome B repair protein. J Biol Chem 273: 11844–11851.

12. LakeRJ, BasheerA, FanHY (2011) Reciprocally regulated chromatin association of Cockayne syndrome protein B and p53 protein. J Biol Chem 286: 34951–34958.

13. 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.

14. BeerensN, HoeijmakersJH, KanaarR, VermeulenW, WymanC (2005) The CSB protein actively wraps DNA. J Biol Chem 280: 4722–4729.

15. YangJG, MadridTS, SevastopoulosE, NarlikarGJ (2006) The chromatin-remodeling enzyme ACF is an ATP-dependent DNA length sensor that regulates nucleosome spacing. Nat Struct Mol Biol 13: 1078–1083.

16. HeX, FanHY, GarlickJD, KingstonRE (2008) Diverse Regulation of SNF2h Chromatin Remodeling by Noncatalytic Subunits. Biochemistry 47: 7025–7033.

17. KristensenU, EpanchintsevA, RauschendorfMA, LaugelV, StevnsnerT, et al. (2013) Regulatory interplay of Cockayne syndrome B ATPase and stress-response gene ATF3 following genotoxic stress. Proc Natl Acad Sci U S A 110: E2261–2270.

18. HanawaltPC, SpivakG (2008) Transcription-coupled DNA repair: two decades of progress and surprises. Nat Rev Mol Cell Biol 9: 958–970.

19. TroelstraC, van GoolA, de WitJ, VermeulenW, BootsmaD, et al. (1992) ERCC6, a member of a subfamily of putative helicases, is involved in Cockayne's syndrome and preferential repair of active genes. Cell 71: 939–953.

20. FousteriM, VermeulenW, van ZeelandAA, MullendersLH (2006) Cockayne syndrome A and B proteins differentially regulate recruitment of chromatin remodeling and repair factors to stalled RNA polymerase II in vivo. Mol Cell 23: 471–482.

21. KyngKJ, MayA, BroshRMJr, ChengWH, ChenC, et al. (2003) The transcriptional response after oxidative stress is defective in Cockayne syndrome group B cells. Oncogene 22: 1135–1149.

22. TuoJ, JarugaP, RodriguezH, BohrVA, DizdarogluM (2003) Primary fibroblasts of Cockayne syndrome patients are defective in cellular repair of 8-hydroxyguanine and 8-hydroxyadenine resulting from oxidative stress. Faseb J 17: 668–674.

23. AamannMD, SorensenMM, HvitbyC, BerquistBR, MuftuogluM, et al. (2010) Cockayne syndrome group B protein promotes mitochondrial DNA stability by supporting the DNA repair association with the mitochondrial membrane. Faseb J 24: 2334–2346.

24. Scheibye-KnudsenM, CroteauDL, BohrVA (2013) Mitochondrial deficiency in Cockayne syndrome. Mech Ageing Dev 134: 275–283.

25. BalajeeAS, MayA, DianovGL, FriedbergEC, BohrVA (1997) Reduced RNA polymerase II transcription in intact and permeabilized Cockayne syndrome group B cells. Proc Natl Acad Sci U S A 94: 4306–4311.

26. BradsherJ, AuriolJ, Proietti de SantisL, IbenS, VoneschJL, et al. (2002) CSB is a component of RNA pol I transcription. Mol Cell 10: 819–829.

27. Vélez-CruzR, EglyJ-M (2013) Cockayne syndrome group B (CSB) protein: At the crossroads of transcriptional networks. Mech Ageing Dev 134: 234–242.

28. NewmanJC, BaileyAD, WeinerAM (2006) Cockayne syndrome group B protein (CSB) plays a general role in chromatin maintenance and remodeling. Proc Natl Acad Sci USA 103: 9613–9618.

29. BaileyAD, GrayLT, PavelitzT, NewmanJC, HoribataK, et al. (2012) The conserved Cockayne syndrome B-piggyBac fusion protein (CSB-PGBD3) affects DNA repair and induces both interferon-like and innate antiviral responses in CSB-null cells. DNA Repair (Amst) 11: 488–501.

30. NewmanJC, BaileyAD, FanHY, PavelitzT, WeinerAM (2008) An abundant evolutionarily conserved CSB-PiggyBac fusion protein expressed in Cockayne syndrome. PLoS Genet 4: e1000031.

31. LangmeadB, TrapnellC, PopM, SalzbergSL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10: R25.

32. ShinH, LiuT, ManraiAK, LiuXS (2009) CEAS: cis-regulatory element annotation system. Bioinformatics 25: 2605–2606.

33. ConsortiumEP (2011) A user's guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol 9: e1001046.

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

35. LakeRJ, GeykoA, HemashettarG, ZhaoY, FanHY (2010) UV-induced association of the CSB remodeling protein with chromatin requires ATP-dependent relief of N-terminal autorepression. Mol Cell 37: 235–246.

36. MalleryDL, TanganelliB, ColellaS, SteingrimsdottirH, van GoolAJ, et al. (1998) Molecular analysis of mutations in the CSB (ERCC6) gene in patients with Cockayne syndrome. Am J Hum Genet 62: 77–85.

37. EferlR, WagnerEF (2003) AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer 3: 859–868.

38. ShaulianE, KarinM (2002) AP-1 as a regulator of cell life and death. Nat Cell Biol 4: E131–136.

39. GrayLT, FongKK, PavelitzT, WeinerAM (2012) Tethering of the Conserved piggyBac Transposase Fusion Protein CSB-PGBD3 to Chromosomal AP-1 Proteins Regulates Expression of Nearby Genes in Humans. PLoS Genet 8: e1002972.

40. Askarian-AmiriME, CrawfordJ, FrenchJD, SmartCE, SmithMA, et al. (2011) SNORD-host RNA Zfas1 is a regulator of mammary development and a potential marker for breast cancer. RNA 17: 878–891.

41. JacksonAP, EastwoodH, BellSM, AduJ, ToomesC, et al. (2002) Identification of microcephalin, a protein implicated in determining the size of the human brain. Am J Hum Genet 71: 136–142.

42. TalkowskiME, RosenfeldJA, BlumenthalI, PillalamarriV, ChiangC, et al. (2012) Sequencing chromosomal abnormalities reveals neurodevelopmental loci that confer risk across diagnostic boundaries. Cell 149: 525–537.

43. IijimaK, YamadaH, MiharuM, ImadomeK, MiyagawaY, et al. (2012) ZNF385B is characteristically expressed in germinal center B cells and involved in B-cell apoptosis. Eur J Immunol 42: 3405–3415.

44. PetrozielloJ, YamaneA, WestendorfL, ThompsonM, McDonaghC, et al. (2004) Suppression subtractive hybridization and expression profiling identifies a unique set of genes overexpressed in non-small-cell lung cancer. Oncogene 23: 7734–7745.

45. OsakiM, InoueT, YamaguchiS, InabaA, TokuyasuN, et al. (2007) MAD1 (mitotic arrest deficiency 1) is a candidate for a tumor suppressor gene in human stomach. Virchows Arch 451: 771–779.

46. LiuY, BoukhelifaM, TribbleE, Morin-KensickiE, UetrechtA, et al. (2008) The Sac1 phosphoinositide phosphatase regulates Golgi membrane morphology and mitotic spindle organization in mammals. Mol Biol Cell 19: 3080–3096.

47. TeeWW, PardoM, TheunissenTW, YuL, ChoudharyJS, et al. (2010) Prmt5 is essential for early mouse development and acts in the cytoplasm to maintain ES cell pluripotency. Genes Dev 24: 2772–2777.

48. MaseratiM, WalentukM, DaiX, HolstonO, AdamsD, et al. (2011) Wdr74 is required for blastocyst formation in the mouse. PLoS One 6: e22516.

49. YaoTW, KimWS, YuDM, SharbeenG, McCaughanGW, et al. (2011) A novel role of dipeptidyl peptidase 9 in epidermal growth factor signaling. Mol Cancer Res 9: 948–959.

50. YadonAN, SinghBN, HampseyM, TsukiyamaT (2013) DNA looping facilitates targeting of a chromatin remodeling enzyme. Mol Cell 50: 93–103.

51. ZhaoW, WangL, ZhangM, WangP, ZhangL, et al. (2011) NF-kappaB- and AP-1-mediated DNA looping regulates osteopontin transcription in endotoxin-stimulated murine macrophages. J Immunol 186: 3173–3179.

52. YadonAN, Van de MarkD, BasomR, DelrowJ, WhitehouseI, et al. (2010) Chromatin remodeling around nucleosome-free regions leads to repression of noncoding RNA transcription. Mol Cell Biol 30: 5110–5122.

53. Mueller-PlanitzF, KlinkerH, BeckerPB (2013) Nucleosome sliding mechanisms: new twists in a looped history. Nat Struct Mol Biol 20: 1026–1032.

54. YuanX, FengW, ImhofA, GrummtI, ZhouY (2007) Activation of RNA polymerase I transcription by cockayne syndrome group B protein and histone methyltransferase G9a. Mol Cell 27: 585–595.

55. BerquistBR, CanugoviC, SykoraP, WilsonDM3rd, BohrVA (2012) Human Cockayne syndrome B protein reciprocally communicates with mitochondrial proteins and promotes transcriptional elongation. Nucleic Acids Res 40: 8392–8405.

56. BrooksPJ, ChengTF, CooperL (2008) Do all of the neurologic diseases in patients with DNA repair gene mutations result from the accumulation of DNA damage? DNA Repair (Amst) 7: 834–848.

57. SchmittgenTD, LivakKJ (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3: 1101–1108.

58. DennisJH, FanHY, ReynoldsSM, YuanG, MeldrimJC, et al. (2007) Independent and complementary methods for large-scale structural analysis of mammalian chromatin. Genome Res 17: 928–939.

59. McLeanCY, BristorD, HillerM, ClarkeSL, SchaarBT, et al. (2010) GREAT improves functional interpretation of cis-regulatory regions. Nat Biotechnol 28: 495–501.

60. FragosoG, HagerGL (1997) Analysis of in vivo nucleosome positions by determination of nucleosome-linker boundaries in crosslinked chromatin. Methods 11: 246–252.

61. ErnstJ, KellisM (2012) ChromHMM: automating chromatin-state discovery and characterization. Nat Meth 9: 215–216.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2014 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#