A Histone Deacetylase Adjusts Transcription Kinetics at Coding Sequences during Morphogenesis

English version České info

Despite their classical role as transcriptional repressors, several histone deacetylases, including the baker's yeast Set3/Hos2 complex (Set3C), facilitate gene expression. In the dimorphic human pathogen Candida albicans, the homologue of the Set3C inhibits the yeast-to-filament transition, but the precise molecular details of this function have remained elusive. Here, we use a combination of ChIP–Seq and RNA–Seq to show that the Set3C acts as a transcriptional co-factor of metabolic and morphogenesis-related genes in C. albicans. Binding of the Set3C correlates with gene expression during fungal morphogenesis; yet, surprisingly, deletion of SET3 leaves the steady-state expression level of most genes unchanged, both during exponential yeast-phase growth and during the yeast-filament transition. Fine temporal resolution of transcription in cells undergoing this transition revealed that the Set3C modulates transient expression changes of key morphogenesis-related genes. These include a transcription factor cluster comprising of NRG1, EFG1, BRG1, and TEC1, which form a regulatory circuit controlling hyphal differentiation. Set3C appears to restrict the factors by modulating their transcription kinetics, and the hyperfilamentous phenotype of SET3-deficient cells can be reverted by mutating the circuit factors. These results indicate that the chromatin status at coding regions represents a dynamic platform influencing transcription kinetics. Moreover, we suggest that transcription at the coding sequence can be transiently decoupled from potentially conflicting promoter information in dynamic environments.

Vyšlo v časopise: A Histone Deacetylase Adjusts Transcription Kinetics at Coding Sequences during Morphogenesis. PLoS Genet 8(12): e32767. doi:10.1371/journal.pgen.1003118
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003118

Souhrn

Zdroje

1. SudberyP, GowN, BermanJ (2004) The distinct morphogenic states of Candida albicans. Trends Microbiol 12: 317–324.

2. ThompsonDS, CarlislePL, KadoshD (2011) Coevolution of morphology and virulence in Candida species. Eukaryot Cell 10: 1173–1182.

3. GowNA, BrownAJ, OddsFC (2002) Fungal morphogenesis and host invasion. Curr Opin Microbiol 5: 366–371.

4. SavilleSP, LazzellAL, BryantAP, FretzenA, MonrealA, et al. (2006) Inhibition of filamentation can be used to treat disseminated candidiasis. Antimicrob Agents Chemother 50: 3312–3316.

5. WhitewayM, BachewichC (2007) Morphogenesis in Candida albicans. Annu Rev Microbiol 61: 529–553.

6. ShapiroRS, RobbinsN, CowenLE (2011) Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol Mol Biol Rev 75: 213–267.

7. NobleSM, FrenchS, KohnLA, ChenV, JohnsonAD (2010) Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity. Nat Genet 42: 590–598.

8. HomannOR, DeaJ, NobleSM, JohnsonAD (2009) A phenotypic profile of the Candida albicans regulatory network. PLoS Genet 5: e1000783.

9. LuY, SuC, MaoX, RanigaPP, LiuH, et al. (2008) Efg1-mediated recruitment of NuA4 to promoters is required for hypha-specific Swi/Snf binding and activation in Candida albicans. Mol Biol Cell 19: 4260–4272.

10. LuY, SuC, WangA, LiuH (2011) Hyphal development in Candida albicans requires two temporally linked changes in promoter chromatin for initiation and maintenance. PLoS Biol 9: e1001105.

11. KadoshD, JohnsonAD (2005) Induction of the Candida albicans filamentous growth program by relief of transcriptional repression: a genome-wide analysis. Mol Biol Cell 16: 2903–2912.

12. LuY, SuC, LiuH (2012) A GATA Transcription Factor Recruits Hda1 in Response to Reduced Tor1 Signaling to Establish a Hyphal Chromatin State in Candida albicans. PLoS Pathog 8: e1002663.

13. RamanSB, NguyenMH, ZhangZ, ChengS, JiaHY, et al. (2006) Candida albicans SET1 encodes a histone 3 lysine 4 methyltransferase that contributes to the pathogenesis of invasive candidiasis. Mol Microbiol 60: 697–709.

14. Lopes da RosaJ, BoyartchukVL, ZhuLJ, KaufmanPD (2010) Histone acetyltransferase Rtt109 is required for Candida albicans pathogenesis. Proc Natl Acad Sci U S A 107: 1594–1599.

15. HniszD, MajerO, FrohnerIE, KomnenovicV, KuchlerK (2010) The Set3/Hos2 histone deacetylase complex attenuates cAMP/PKA signaling to regulate morphogenesis and virulence of Candida albicans. PLoS Pathog 6: e1000889.

16. PijnappelWW, SchaftD, RoguevA, ShevchenkoA, TekotteH, et al. (2001) The S. cerevisiae SET3 complex includes two histone deacetylases, Hos2 and Hst1, and is a meiotic-specific repressor of the sporulation gene program. Genes Dev 15: 2991–3004.

17. WangA, KurdistaniSK, GrunsteinM (2002) Requirement of Hos2 histone deacetylase for gene activity in yeast. Science 298: 1412–1414.

18. KimT, BuratowskiS (2009) Dimethylation of H3K4 by Set1 recruits the Set3 histone deacetylase complex to 5′ transcribed regions. Cell 137: 259–272.

19. LiuOW, ChunCD, ChowED, ChenC, MadhaniHD, et al. (2008) Systematic genetic analysis of virulence in the human fungal pathogen Cryptococcus neoformans. Cell 135: 174–188.

20. DingSL, LiuW, IliukA, RibotC, ValletJ, et al. (2010) The tig1 histone deacetylase complex regulates infectious growth in the rice blast fungus Magnaporthe oryzae. Plant Cell 22: 2495–2508.

21. ZhangY, LiuT, MeyerCA, EeckhouteJ, JohnsonDS, et al. (2008) Model-based analysis of ChIP-Seq (MACS). Genome Biol 9: R137.

22. NantelA, DignardD, BachewichC, HarcusD, MarcilA, et al. (2002) Transcription profiling of Candida albicans cells undergoing the yeast-to-hyphal transition. Mol Biol Cell 13: 3452–3465.

23. NobileCJ, FoxEP, NettJE, SorrellsTR, MitrovichQM, et al. (2012) A recently evolved transcriptional network controls biofilm development in Candida albicans. Cell 148: 126–138.

24. NobileCJ, NettJE, HerndayAD, HomannOR, DeneaultJS, et al. (2009) Biofilm matrix regulation by Candida albicans Zap1. PLoS Biol 7: e1000133.

25. AskewC, SellamA, EppE, HoguesH, MullickA, et al. (2009) Transcriptional regulation of carbohydrate metabolism in the human pathogen Candida albicans. PLoS Pathog 5: e1000612.

26. LavoieH, HoguesH, MallickJ, SellamA, NantelA, et al. (2010) Evolutionary tinkering with conserved components of a transcriptional regulatory network. PLoS Biol 8: e1000329.

27. LassakT, SchneiderE, BussmannM, KurtzD, ManakJR, et al. (2011) Target specificity of the Candida albicans Efg1 regulator. Mol Microbiol 82: 602–618.

28. UhlMA, BieryM, CraigN, JohnsonAD (2003) Haploinsufficiency-based large-scale forward genetic analysis of filamentous growth in the diploid human fungal pathogen C.albicans. EMBO J 22: 2668–2678.

29. MouZ, KennyAE, CurcioMJ (2006) Hos2 and Set3 promote integration of Ty1 retrotransposons at tRNA genes in Saccharomyces cerevisiae. Genetics 172: 2157–2167.

30. LenstraTL, BenschopJJ, KimT, SchulzeJM, BrabersNA, et al. (2011) The specificity and topology of chromatin interaction pathways in yeast. Mol Cell 42: 536–549.

31. WeinerA, ChenHV, LiuCL, RahatA, KlienA, et al. (2012) Systematic dissection of roles for chromatin regulators in a yeast stress response. PLoS Biol 10: e1001369.

32. LeeJS, SmithE, ShilatifardA (2010) The language of histone crosstalk. Cell 142: 682–685.

33. HenikoffS, ShilatifardA (2011) Histone modification: cause or cog? Trends Genet 27: 389–396.

34. Alejandro-OsorioAL, HuebertDJ, PorcaroDT, SonntagME, NillasithanukrohS, et al. (2009) The histone deacetylase Rpd3p is required for transient changes in genomic expression in response to stress. Genome Biol 10: R57.

35. LohseMB, JohnsonAD (2010) Temporal anatomy of an epigenetic switch in cell programming: the white-opaque transition of C. albicans. Mol Microbiol 78: 331–343.

36. SellamA, HoguesH, AskewC, TebbjiF, van Het HoogM, et al. (2010) Experimental annotation of the human pathogen Candida albicans coding and noncoding transcribed regions using high-resolution tiling arrays. Genome Biol 11: R71.

37. BuratowskiS (2009) Progression through the RNA polymerase II CTD cycle. Mol Cell 36: 541–546.

38. EgloffS, MurphyS (2008) Cracking the RNA polymerase II CTD code. Trends Genet 24: 280–288.

39. EgloffS, DienstbierM, MurphyS (2012) Updating the RNA polymerase CTD code: adding gene-specific layers. Trends Genet

40. KimT, XuZ, Clauder-MünsterS, SteinmetzL, BuratowskiS (2012) Set3 HDAC mediates effects of overlapping noncoding transcription on gene induction kinetics. Cell doi:10.1016/j.cell.2012.08.016.

41. NobleSM, JohnsonAD (2005) Strains and strategies for large-scale gene deletion studies of the diploid human fungal pathogen Candida albicans. Eukaryot Cell 4: 298–309.

42. FrohnerIE, BourgeoisC, YatsykK, MajerO, KuchlerK (2009) Candida albicans cell surface superoxide dismutases degrade host-derived reactive oxygen species to escape innate immune surveillance. Mol Microbiol 71: 240–252.

43. ReussO, VikA, KolterR, MorschhauserJ (2004) The SAT1 flipper, an optimized tool for gene disruption in Candida albicans. Gene 341: 119–127.

44. HerndayAD, NobleSM, MitrovichQM, JohnsonAD (2010) Genetics and molecular biology in Candida albicans. Methods Enzymol 470: 737–758.

45. TrapnellC, PachterL, SalzbergSL (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25: 1105–1111.

46. TrapnellC, WilliamsBA, PerteaG, MortazaviA, KwanG, et al. (2010) Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol 28: 511–515.

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

48. MortazaviA, WilliamsBA, McCueK, SchaefferL, WoldB (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 5: 621–628.

49. LiH, FischleW, WangW, DuncanEM, LiangL, et al. (2007) Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger. Mol Cell 28: 677–691.

50. SaliA, BlundellTL (1993) Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234: 779–815.