The conserved regulatory basis of mRNA contributions to the early Drosophila embryo differs between the maternal and zygotic genomes
Autoři:
Charles S. Omura aff001; Susan E. Lott aff001
Působiště autorů:
Department of Evolution and Ecology, University of California, Davis, Davis, California, United States of America
aff001
Vyšlo v časopise:
The conserved regulatory basis of mRNA contributions to the early Drosophila embryo differs between the maternal and zygotic genomes. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008645
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008645
Souhrn
The gene products that drive early development are critical for setting up developmental trajectories in all animals. The earliest stages of development are fueled by maternally provided mRNAs until the zygote can take over transcription of its own genome. In early development, both maternally deposited and zygotically transcribed gene products have been well characterized in model systems. Previously, we demonstrated that across the genus Drosophila, maternal and zygotic mRNAs are largely conserved but also showed a surprising amount of change across species, with more differences evolving at the zygotic stage than the maternal stage. In this study, we use comparative methods to elucidate the regulatory mechanisms underlying maternal deposition and zygotic transcription across species. Through motif analysis, we discovered considerable conservation of regulatory mechanisms associated with maternal transcription, as compared to zygotic transcription. We also found that the regulatory mechanisms active in the maternal and zygotic genomes are quite different. For maternally deposited genes, we uncovered many signals that are consistent with transcriptional regulation at the level of chromatin state through factors enriched in the ovary, rather than precisely controlled gene-specific factors. For genes expressed only by the zygotic genome, we found evidence for previously identified regulators such as Zelda and GAGA-factor, with multiple analyses pointing toward gene-specific regulation. The observed mechanisms of regulation are consistent with what is known about regulation in these two genomes: during oogenesis, the maternal genome is optimized to quickly produce a large volume of transcripts to provide to the oocyte; after zygotic genome activation, mechanisms are employed to activate transcription of specific genes in a spatiotemporally precise manner. Thus the genetic architecture of the maternal and zygotic genomes, and the specific requirements for the transcripts present at each stage of embryogenesis, determine the regulatory mechanisms responsible for transcripts present at these stages.
Klíčová slova:
DNA transcription – Drosophila melanogaster – Gene expression – Gene regulation – Chromatin – Invertebrate genomics – Sequence motif analysis – Transcriptional control
Zdroje
1. Driever W, Nüsslein-Volhard C. The bicoid protein determines position in the Drosophila embryo in a concentration-dependent manner. Cell. 1988;54: 95–104. doi: 10.1016/0092-8674(88)90183-3 3383245
2. Lécuyer E, Yoshida H, Parthasarathy N, Alm C, Babak T, Cerovina T, et al. Global analysis of mRNA localization reveals a prominent role in organizing cellular architecture and function. Cell. 2007;131: 174–187. doi: 10.1016/j.cell.2007.08.003 17923096
3. Vastenhouw NL, Cao WX, Lipshitz HD. The maternal-to-zygotic transition revisited. Development. 2019;146. doi: 10.1242/dev.161471 31189646
4. Schulz KN, Harrison MM. Mechanisms regulating zygotic genome activation. Nat Rev Genet. 2019;20: 221–234. doi: 10.1038/s41576-018-0087-x 30573849
5. Ventos‐Alfonso A, Ylla G, Belles X. Zelda and the maternal‐to‐zygotic transition in cockroaches. FEBS J. 2019. doi: 10.1111/febs.14856 30993896
6. Navarro-Costa P, McCarthy A, Prudêncio P, Greer C, Guilgur LG, Becker JD, et al. Early programming of the oocyte epigenome temporally controls late prophase I transcription and chromatin remodelling. Nat Commun. 2016;7: 12331. doi: 10.1038/ncomms12331 27507044
7. Mische S, Li M, Serr M, Hays TS. Direct observation of regulated ribonucleoprotein transport across the nurse cell/oocyte boundary. Mol Biol Cell. 2007;18: 2254–2263. doi: 10.1091/mbc.E06-10-0959 17429069
8. Tadros W, Westwood JT, Lipshitz HD. The mother-to-child transition. Dev Cell. 2007;12: 847–849. doi: 10.1016/j.devcel.2007.05.009 17543857
9. Liang H-L, Nien C-Y, Liu H-Y, Metzstein MM, Kirov N, Rushlow C. The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila. Nature. 2008;456: 400–403. doi: 10.1038/nature07388 18931655
10. Harrison MM, Li X-Y, Kaplan T, Botchan MR, Eisen MB. Zelda binding in the early Drosophila melanogaster embryo marks regions subsequently activated at the maternal-to-zygotic transition. PLoS Genet. 2011;7: e1002266. doi: 10.1371/journal.pgen.1002266 22028662
11. Akam M. The molecular basis for metameric pattern in the Drosophila embryo. Development. 1987;101: 1–22.
12. Ingham PW. The molecular genetics of embryonic pattern formation in Drosophila. Nature. 1988;335: 25–34. doi: 10.1038/335025a0 2901040
13. Tadros W, Goldman AL, Babak T, Menzies F, Vardy L, Orr-Weaver T, et al. SMAUG is a major regulator of maternal mRNA destabilization in Drosophila and its translation is activated by the PAN GU kinase. Dev Cell. 2007;12: 143–155. doi: 10.1016/j.devcel.2006.10.005 17199047
14. Benoit B, He CH, Zhang F, Votruba SM, Tadros W, Westwood JT, et al. An essential role for the RNA-binding protein Smaug during the Drosophila maternal-to-zygotic transition. Development. 2009;136: 923–932. doi: 10.1242/dev.031815 19234062
15. Laver JD, Li X, Ray D, Cook KB, Hahn NA, Nabeel-Shah S, et al. Brain tumor is a sequence-specific RNA-binding protein that directs maternal mRNA clearance during the Drosophila maternal-to-zygotic transition. Genome Biol. 2015;16: 94. doi: 10.1186/s13059-015-0659-4 25962635
16. Bushati N, Stark A, Brennecke J, Cohen SM. Temporal reciprocity of miRNAs and their targets during the maternal-to-zygotic transition in Drosophila. Curr Biol. 2008;18: 501–506. doi: 10.1016/j.cub.2008.02.081 18394895
17. Becalska AN, Gavis ER. Lighting up mRNA localization in Drosophila oogenesis. Development. 2009;136: 2493–2503. doi: 10.1242/dev.032391 19592573
18. Clark A, Meignin C, Davis I. A Dynein-dependent shortcut rapidly delivers axis determination transcripts into the Drosophila oocyte. Development. 2007;134: 1955–1965. doi: 10.1242/dev.02832 17442699
19. Barckmann B, Simonelig M. Control of maternal mRNA stability in germ cells and early embryos. Biochim Biophys Acta. 2013;1829: 714–724. doi: 10.1016/j.bbagrm.2012.12.011 23298642
20. Cui J, Sackton KL, Horner VL, Kumar KE, Wolfner MF. Wispy, the Drosophila homolog of GLD-2, is required during oogenesis and egg activation. Genetics. 2008;178: 2017–2029. doi: 10.1534/genetics.107.084558 18430932
21. Benoit P, Papin C, Kwak JE, Wickens M, Simonelig M. PAP- and GLD-2-type poly(A) polymerases are required sequentially in cytoplasmic polyadenylation and oogenesis in Drosophila. Development. 2008;135: 1969–1979. doi: 10.1242/dev.021444 18434412
22. Sallés FJ, Lieberfarb ME, Wreden C, Gergen JP, Strickland S. Coordinate initiation of Drosophila development by regulated polyadenylation of maternal messenger RNAs. Science. 1994;266: 1996–1999. doi: 10.1126/science.7801127 7801127
23. Temme C, Simonelig M, Wahle E. Deadenylation of mRNA by the CCR4-NOT complex in Drosophila: molecular and developmental aspects. Front Genet. 2014;5: 143. doi: 10.3389/fgene.2014.00143 24904643
24. Atallah J, Lott SE. Evolution of maternal and zygotic mRNA complements in the early Drosophila embryo. PLoS Genet. 2018;14: e1007838. doi: 10.1371/journal.pgen.1007838 30557299
25. Bownes M. A photographic study of development in the living embryo of Drosophila melanogaster. J Embryol Exp Morphol. 1975;33: 789–801. 809527
26. Campos-Ortega JA, Hartenstein V. The Embryonic Development of Drosophila melanogaster. Springer, Berlin, Heidelberg; 1985.
27. Nègre N, Brown CD, Ma L, Bristow CA, Miller SW, Wagner U, et al. A cis-regulatory map of the Drosophila genome. Nature. 2011;471: 527–531. doi: 10.1038/nature09990 21430782
28. Clark AG, Eisen MB, Smith DR, Bergman CM, Oliver B, Markow TA, et al. Evolution of genes and genomes on the Drosophila phylogeny. Nature. 2007;450: 203–218. doi: 10.1038/nature06341 17994087
29. Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38: 576–589. doi: 10.1016/j.molcel.2010.05.004 20513432
30. De Renzis S, Elemento O, Tavazoie S, Wieschaus EF. Unmasking activation of the zygotic genome using chromosomal deletions in the Drosophila embryo. PLoS Biol. 2007;5: e117. doi: 10.1371/journal.pbio.0050117 17456005
31. Thomsen S, Anders S, Janga SC, Huber W, Alonso CR. Genome-wide analysis of mRNA decay patterns during early Drosophila development. Genome Biol. 2010;11: R93. doi: 10.1186/gb-2010-11-9-r93 20858238
32. Lott SE, Villalta JE, Zhou Q, Bachtrog D, Eisen MB. Sex-specific embryonic gene expression in species with newly evolved sex chromosomes. PLoS Genet. 2014;10: e1004159. doi: 10.1371/journal.pgen.1004159 24550743
33. Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L, et al. MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res. 2009;37: W202–8. doi: 10.1093/nar/gkp335 19458158
34. Ramírez F, Bhardwaj V, Arrigoni L, Lam KC, Grüning BA, Villaveces J, et al. High-resolution TADs reveal DNA sequences underlying genome organization in flies. Nat Commun. 2018;9: 189. doi: 10.1038/s41467-017-02525-w 29335486
35. Zabidi MA, Arnold CD, Schernhuber K, Pagani M, Rath M, Frank O, et al. Enhancer-core-promoter specificity separates developmental and housekeeping gene regulation. Nature. 2015;518: 556–559. doi: 10.1038/nature13994 25517091
36. Chen K, Johnston J, Shao W, Meier S, Staber C, Zeitlinger J. A global change in RNA polymerase II pausing during the Drosophila midblastula transition. Elife. 2013;2: e00861. doi: 10.7554/eLife.00861 23951546
37. Liu MM, Davey JW, Jackson DJ, Blaxter ML, Davison A. A conserved set of maternal genes? Insights from a molluscan transcriptome. Int J Dev Biol. 2014;58: 501–511. doi: 10.1387/ijdb.140121ad 25690965
38. Ghavi-Helm Y. Functional consequences of chromosomal rearrangements on gene expression: not so deleterious after all? J Mol Biol. 2019. doi: 10.1016/j.jmb.2019.09.010 31626801
39. Matsukage A, Hirose F, Yoo M-A, Yamaguchi M. The DRE/DREF transcriptional regulatory system: a master key for cell proliferation. Biochim Biophys Acta. 2008;1779: 81–89. doi: 10.1016/j.bbagrm.2007.11.011 18155677
40. Yang J, Ramos E, Corces VG. The BEAF-32 insulator coordinates genome organization and function during the evolution of Drosophila species. Genome Res. 2012;22: 2199–2207. doi: 10.1101/gr.142125.112 22895281
41. Nègre N, Brown CD, Shah PK, Kheradpour P, Morrison CA, Henikoff JG, et al. A comprehensive map of insulator elements for the Drosophila genome. PLoS Genet. 2010;6: e1000814. doi: 10.1371/journal.pgen.1000814 20084099
42. Maksimenko O, Bartkuhn M, Stakhov V, Herold M, Zolotarev N, Jox T, et al. Two new insulator proteins, Pita and ZIPIC, target CP190 to chromatin. Genome Res. 2015;25: 89–99. doi: 10.1101/gr.174169.114 25342723
43. Li J, Gilmour DS. Distinct mechanisms of transcriptional pausing orchestrated by GAGA factor and M1BP, a novel transcription factor. EMBO J. 2013;32: 1829–1841. doi: 10.1038/emboj.2013.111 23708796
44. Levine M. Paused RNA polymerase II as a developmental checkpoint. Cell. 2011;145: 502–511. doi: 10.1016/j.cell.2011.04.021 21565610
45. Benyajati C, Mueller L, Xu N, Pappano M, Gao J, Mosammaparast M, et al. Multiple isoforms of GAGA factor, a critical component of chromatin structure. Nucleic Acids Res. 1997;25: 3345–3353. doi: 10.1093/nar/25.16.3345 9241251
46. Tsai S-Y, Chang Y-L, Swamy KBS, Chiang R-L, Huang D-H. GAGA factor, a positive regulator of global gene expression, modulates transcriptional pausing and organization of upstream nucleosomes. Epigenetics Chromatin. 2016;9: 32. doi: 10.1186/s13072-016-0082-4 27468311
47. Granok H, Leibovitch BA, Shaffer CD, Elgin SC. Chromatin. Ga-ga over GAGA factor. Curr Biol. 1995;5: 238–241. doi: 10.1016/s0960-9822(95)00048-0 7780729
48. Harrison MM, Botchan MR, Cline TW. Grainyhead and Zelda compete for binding to the promoters of the earliest-expressed Drosophila genes. Dev Biol. 2010;345: 248–255. doi: 10.1016/j.ydbio.2010.06.026 20599892
49. Schulz KN, Bondra ER, Moshe A, Villalta JE, Lieb JD, Kaplan T, et al. Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo. Genome Res. 2015;25: 1715–1726. doi: 10.1101/gr.192682.115 26335634
50. Sun Y, Nien C-Y, Chen K, Liu H-Y, Johnston J, Zeitlinger J, et al. Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation. Genome Res. 2015;25: 1703–1714. doi: 10.1101/gr.192542.115 26335633
51. Ohler U, Liao G-C, Niemann H, Rubin GM. Computational analysis of core promoters in the Drosophila genome. Genome Biol. 2002;3: RESEARCH0087.
52. Lis M, Walther D. The orientation of transcription factor binding site motifs in gene promoter regions: does it matter? BMC Genomics. 2016;17: 185. doi: 10.1186/s12864-016-2549-x 26939991
53. Yu G, Wang L-G, Han Y, He Q-Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012;16: 284–287. doi: 10.1089/omi.2011.0118 22455463
54. R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2014. Available: http://www.R-project.org/
55. Brown JB, Boley N, Eisman R, May GE, Stoiber MH, Duff MO, et al. Diversity and dynamics of the Drosophila transcriptome. Nature. 2014;512: 393–399. doi: 10.1038/nature12962 24670639
56. Leader DP, Krause SA, Pandit A, Davies SA, Dow JAT. FlyAtlas 2: a new version of the Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data. Nucleic Acids Res. 2018;46: D809–D815. doi: 10.1093/nar/gkx976 29069479
57. Vogel C, Marcotte EM. Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat Rev Genet. 2012;13: 227–232. doi: 10.1038/nrg3185 22411467
58. Graveley BR, Brooks AN, Carlson JW, Duff MO, Landolin JM, Yang L, et al. The developmental transcriptome of Drosophila melanogaster. Nature. 2011;471: 473–479. doi: 10.1038/nature09715 21179090
59. modENCODE Consortium, Roy S, Ernst J, Kharchenko PV, Kheradpour P, Negre N, et al. Identification of functional elements and regulatory circuits by Drosophila modENCODE. Science. 2010;330: 1787–1797. doi: 10.1126/science.1198374 21177974
60. Bauke A-C, Sasse S, Matzat T, Klämbt C. A transcriptional network controlling glial development in the Drosophila visual system. Development. 2015;142: 2184–2193. doi: 10.1242/dev.119750 26015542
61. Gurudatta BV, Yang J, Van Bortle K, Donlin-Asp PG, Corces VG. Dynamic changes in the genomic localization of DNA replication-related element binding factor during the cell cycle. Cell Cycle. 2013;12: 1605–1615. doi: 10.4161/cc.24742 23624840
62. Ulianov SV, Khrameeva EE, Gavrilov AA, Flyamer IM, Kos P, Mikhaleva EA, et al. Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains. Genome Res. 2016;26: 70–84. doi: 10.1101/gr.196006.115 26518482
63. Hou C, Li L, Qin ZS, Corces VG. Gene density, transcription, and insulators contribute to the partition of the Drosophila genome into physical domains. Mol Cell. 2012;48: 471–484. doi: 10.1016/j.molcel.2012.08.031 23041285
64. Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, et al. NCBI GEO: archive for functional genomics data sets—update. Nucleic Acids Res. 2013;41: D991–5. doi: 10.1093/nar/gks1193 23193258
65. Bradley JV. Distribution-free statistical tests. Prentice-Hall; 1968.
66. Artieri CG, Fraser HB. Transcript length mediates developmental timing of gene expression across Drosophila. Mol Biol Evol. 2014;31: 2879–2889. doi: 10.1093/molbev/msu226 25069653
67. Heyn P, Kircher M, Dahl A, Kelso J, Tomancak P, Kalinka AT, et al. The earliest transcribed zygotic genes are short, newly evolved, and different across species. Cell Rep. 2014;6: 285–292. doi: 10.1016/j.celrep.2013.12.030 24440719
68. Zhang L, Kasif S, Cantor CR, Broude NE. GC/AT-content spikes as genomic punctuation marks. Proc Natl Acad Sci U S A. 2004;101: 16855–16860. doi: 10.1073/pnas.0407821101 15548610
69. Naughton C, Avlonitis N, Corless S, Prendergast JG, Mati IK, Eijk PP, et al. Transcription forms and remodels supercoiling domains unfolding large-scale chromatin structures. Nat Struct Mol Biol. 2013;20: 387–395. doi: 10.1038/nsmb.2509 23416946
70. Pedone F, Filetici P, Ballario P. Yeast RNA polymerase II transcription of circular DNA at different degrees of supercoiling. Nucleic Acids Res. 1982;10: 5197–5208. doi: 10.1093/nar/10.17.5197 6292834
71. Matsumoto K, Hirose S. Visualization of unconstrained negative supercoils of DNA on polytene chromosomes of Drosophila. J Cell Sci. 2004;117: 3797–3805. doi: 10.1242/jcs.01225 15252118
72. Vlijm R, V D Torre J, Dekker C. Counterintuitive DNA Sequence Dependence in Supercoiling-Induced DNA Melting. PLoS One. 2015;10: e0141576. doi: 10.1371/journal.pone.0141576 26513573
73. Tadros W, Lipshitz HD. The maternal-to-zygotic transition: a play in two acts. Development. 2009;136: 3033–3042. doi: 10.1242/dev.033183 19700615
74. Van Bortle K, Nichols MH, Li L, Ong C-T, Takenaka N, Qin ZS, et al. Insulator function and topological domain border strength scale with architectural protein occupancy. Genome Biol. 2014;15: R82. doi: 10.1186/gb-2014-15-5-r82 24981874
75. Ghavi-Helm Y, Jankowski A, Meiers S, Viales RR, Korbel JO, Furlong EEM. Highly rearranged chromosomes reveal uncoupling between genome topology and gene expression. Nat Genet. 2019;51: 1272–1282. doi: 10.1038/s41588-019-0462-3 31308546
76. Despang A, Schöpflin R, Franke M, Ali S, Jerković I, Paliou C, et al. Functional dissection of the Sox9-Kcnj2 locus identifies nonessential and instructive roles of TAD architecture. Nat Genet. 2019;51: 1263–1271. doi: 10.1038/s41588-019-0466-z 31358994
77. Jambor H, Surendranath V, Kalinka AT, Mejstrik P, Saalfeld S, Tomancak P. Systematic imaging reveals features and changing localization of mRNAs in Drosophila development. Elife. 2015;4. doi: 10.7554/eLife.05003 25838129
78. Dej KJ, Spradling AC. The endocycle controls nurse cell polytene chromosome structure during Drosophila oogenesis. Development. 1999;126: 293–303. 9847243
79. Zhimulev IF, Belyaeva ES, Semeshin VF, Koryakov DE, Demakov SA, Demakova OV, et al. Polytene Chromosomes: 70 Years of Genetic Research. International Review of Cytology. Academic Press; 2004. pp. 203–275. doi: 10.1016/S0074-7696(04)41004-3 15548421
80. Abruzzi K, Chen X, Nagoshi E, Zadina A, Rosbash M. Chapter Seventeen—RNA-seq Profiling of Small Numbers of Drosophila Neurons. In: Sehgal A, editor. Methods in Enzymology. Academic Press; 2015. pp. 369–386. doi: 10.1016/bs.mie.2014.10.025 25662465
81. Liang J, Lacroix L, Gamot A, Cuddapah S, Queille S, Lhoumaud P, et al. Chromatin immunoprecipitation indirect peaks highlight long-range interactions of insulator proteins and Pol II pausing. Mol Cell. 2014;53: 672–681. doi: 10.1016/j.molcel.2013.12.029 24486021
82. Phillips-Cremins JE, Corces VG. Chromatin insulators: linking genome organization to cellular function. Mol Cell. 2013;50: 461–474. doi: 10.1016/j.molcel.2013.04.018 23706817
83. Matzat LH, Lei EP. Surviving an identity crisis: a revised view of chromatin insulators in the genomics era. Biochim Biophys Acta. 2014;1839: 203–214. doi: 10.1016/j.bbagrm.2013.10.007 24189492
84. Matzat LH, Dale RK, Moshkovich N, Lei EP. Tissue-specific regulation of chromatin insulator function. PLoS Genet. 2012;8: e1003069. doi: 10.1371/journal.pgen.1003069 23209434
85. Vardy L, Orr-Weaver TL. Regulating translation of maternal messages: multiple repression mechanisms. Trends Cell Biol. 2007;17: 547–554. doi: 10.1016/j.tcb.2007.09.002 18029182
86. Gramates LS, Marygold SJ, Santos GD, Urbano J-M, Antonazzo G, Matthews BB, et al. FlyBase at 25: looking to the future. Nucleic Acids Res. 2017;45: D663–D671. doi: 10.1093/nar/gkw1016 27799470
87. Brooks MJ, Rajasimha HK, Roger JE, Swaroop A. Next-generation sequencing facilitates quantitative analysis of wild-type and Nrl(-/-) retinal transcriptomes. Mol Vis. 2011;17: 3034–3054. 22162623
88. Tao T, Zhao L, Lv Y, Chen J, Hu Y, Zhang T, et al. Transcriptome sequencing and differential gene expression analysis of delayed gland morphogenesis in Gossypium australe during seed germination. PLoS One. 2013;8: e75323. doi: 10.1371/journal.pone.0075323 24073262
89. Cock PJA, Antao T, Chang JT, Chapman BA, Cox CJ, Dalke A, et al. Biopython: freely available Python tools for computational molecular biology and bioinformatics. Bioinformatics. 2009;25: 1422–1423. doi: 10.1093/bioinformatics/btp163 19304878
90. Medina-Rivera A, Defrance M, Sand O, Herrmann C, Castro-Mondragon JA, Delerce J, et al. RSAT 2015: Regulatory Sequence Analysis Tools. Nucleic Acids Res. 2015;43: W50–6. doi: 10.1093/nar/gkv362 25904632
91. Khan A, Fornes O, Stigliani A, Gheorghe M, Castro-Mondragon JA, van der Lee R, et al. JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework. Nucleic Acids Res. 2018;46: D260–D266. doi: 10.1093/nar/gkx1126 29140473
92. Jones E, Oliphant T, Peterson P, Others. SciPy: Open source scientific tools for Python. Available: http://www.scipy.org/
93. Carlson M. org.Dm.eg.db: Genome wide annotation for Fly. 2018.
94. Venables WN, Ripley BD. Modern Applied Statistics with S. New York: Springer; 2002. Available: http://www.stats.ox.ac.uk/pub/MASS4
Článek vyšel v časopise
PLOS Genetics
2020 Číslo 3
- Může hubnutí souviset s vyšším rizikem nádorových onemocnění?
- Raději si zajděte na oční! Jak souvisí citlivost zraku s rozvojem demence?
- Co způsobuje pooperační infekce? Na vině může být i naše vlastní mikrobiota
- Čeká nás průlom v diagnostice karcinomu pankreatu?
- Polibek, který mi „vzal nohy“ aneb vzácný výskyt EBV u 70leté ženy – kazuistika
Nejčtenější v tomto čísle
- Evidence of defined temporal expression patterns that lead a gram-negative cell out of dormancy
- The Lid/KDM5 histone demethylase complex activates a critical effector of the oocyte-to-zygote transition
- The alarmones (p)ppGpp are part of the heat shock response of Bacillus subtilis
- Modeling cancer genomic data in yeast reveals selection against ATM function during tumorigenesis