A modeling framework for generation of positional and temporal simulations of transcriptional regulation
Pages 459 - 471
Abstract
We present a modeling framework aimed at capturing both the positional and temporal behavior of transcriptional regulatory proteins in eukaryotic cells. There is growing evidence that transcriptional regulation is the complex behavior that emerges not solely from the individual components, but rather from their collective behavior, including competition and cooperation. Our framework describes individual regulatory components using generic action oriented descriptions of their biochemical interactions with a DNA sequence. All the possible actions are based on the current state of factors bound to the DNA. We developed a rule builder to automatically generate the complete set of biochemical interaction rules for any given DNA sequence. Off-the-shelf stochastic simulation engines can model the behavior of a system of rules and the resulting changes in the configuration of bound factors can be visualized. We compared our model to experimental data at well-studied loci in yeast, confirming that our model captures both the positional and temporal behavior of transcriptional regulation.
References
[1]
P. J. Farnham, "Insights from genomic profiling of transcription factors," Nature Rev. Genetics, vol. 10, no. 9, pp. 605--616, Sep. 2009.
[2]
A. H. Mack, D. J. Schlingman, R. P. Ilagan, L. Regan, and S. G. J. Mochrie. (2012, Nov.). Kinetics and thermodynamics of pheno-type: Unwinding and rewinding the nucleosome. J. Molecular Biol. {Online}. 423(5), pp. 687--01. Available: http://www.ncbi.nlm.nih.gov/ /22944905
[3]
X. Darzacq, Y. Shav-Tal, V. de Turris, Y. Brody, S. M. Shenoy, R. D. Phair, and R. H. Singer. (2007, Sep.). In vivo dynamics of RNA polymerase II transcription. Nature Structural & Molecular Biol. {Online}. 14(9), pp. 796--806. Available: http://www.ncbi.nlm.nih.gov/ /17676063
[4]
L. A. Mirny, "Nucleosome-mediated cooperativity between transcription factors," Proc. Nat. Acad. Sci. USA, vol. 107, no. 52, pp. 22 534--22 539, Dec. 2010.
[5]
L. Bai, A. Ondracka, and F. R. Cross, "multiple sequence-specific factors generate the nucleosome-depleted region on CLN2 promoter," Molecular Cell, vol. 42, no. 4, pp. 465--476, May 2011.
[6]
S. Hahn and E. T. Young, "Transcriptional regulation in saccharo-myces cerevisiae: Transcription factor regulation and function, mechanisms of initiation, and roles of activators and coac-tivators," Genetics, vol. 189, no. 3, pp. 705--736, Nov. 2011.
[7]
A. C. Palmer, J. B. Egan, and K. E. Shearwin, "Transcriptional interference by RNA polymerase pausing and dislodgement of transcription factors," Transcription, vol. 2, no. 1, pp. 9--14, Jan. 2011.
[8]
E. Segal, Y. Fondufe-Mittendorf, L. Chen, A. Thåström, Y. Field, I. K. Moore, J.-P. Z. Wang, and J. Widom, "A genomic code for nucleosome positioning," Nature, vol. 442, no. 7104, pp. 772--778, Aug. 2006.
[9]
B. J. Venters, S. Wachi, T. N. Mavrich, B. E. Andersen, P. Jena, A. J. Sinnamon, P. Jain, N. S. Rolleri, C. Jiang, C. Hemeryck-Walsh, and B. F. Pugh, "A comprehensive genomic binding map of gene and chromatin regulatory proteins in Saccharomyces," Molecular Cell, vol. 41, no. 4, pp. 480--492, Feb. 2011.
[10]
R. K. Bradley, X.-Y. Li, C. Trapnell, S. Davidson, L. Pachter, H. C. Chu, L. A. Tonkin, M. D. Biggin, and M. B. Eisen, "Binding site turnover produces pervasive quantitative changes in transcription factor binding between closely related Drosophila species," PLoS Biol., vol. 8, no. 3, p. e1000343, Mar. 2010.
[11]
C. R. Lickwar, F. Mueller, S. E. Hanlon, J. G. McNally, and J. D. Lieb, "Genome-wide proteinDNA binding dynamics suggest a molecular clutch for transcription factor function," Nature, vol. 484, no. 7393, pp. 251--255, Apr. 2012.
[12]
J. M. Levsky, S. M. Shenoy, R. C. Pezo, and R. H. Singer. (2002, Aug.). Single-cell gene expression profiling. Science {Online}. 297 (5582), pp. 836--40. Available: http://www.ncbi.nlm.nih.gov/ /12161654
[13]
E. A. Galburt, S. W. Grill, and C. Bustamante. (2009, Aug.). Single molecule transcription elongation. Methods {Online}. 48(4), pp. 323--332. Available: http://www.ncbi.nlm.nih.gov/ /19426807
[14]
Y. Taniguchi, P. J. Choi, G.-W. Li, H. Chen, M. Babu, J. Hearn, A. Emili, and X. S. Xie, "Quantifying E. coli proteome and transcrip-tome with single-molecule sensitivity in single cells," Science, vol. 329, no. 5991, pp. 533--538, Jul. 2010.
[15]
D. R. Larson, D. Zenklusen, B. Wu, J. A. Chao, and R. H. Singer. (2011, Apr.). Real-time observation of transcription initiation and elongation on an endogenous yeast gene. Science {Online}. 332 (6028), pp. 475--478. Available: http://www.ncbi.nlm.nih.gov/ /21512033
[16]
E. Segal and J. Widom. (2009, Jul.). From DNA sequence to transcriptional behaviour: a quantitative approach. Nature Rev. Genetics {Online}. 10(7), pp. 443--56. Available: http://www.ncbi.nlm. nih.gov/ /19506578
[17]
K. Struhl and E. Segal. (2013, Mar.). Determinants of nucleosome positioning. Nature Structural & Molecular Biol. {Online}. 20(3), pp. 267--73. Available: http://www.nature.com/doifinder/10.1038/nsmb.2506
[18]
A. Sanchez, H. G. Garcia, D. Jones, R. Phillips, and J. Kondev, "Effect of promoter architecture on the cell-to-cell variability in gene expression," PLoS Comput. Biol., vol. 7, no. 3, p. e1001100, Mar. 2011.
[19]
T.-L. To and N. Maheshri. (2010, Feb.). Noise can induce bimodal-ity in positive transcriptional feedback loops without bistability. Science {Online}. 327(5969), pp. 1142--1145. Available: http://www.ncbi.nlm.nih.gov/ /20185727
[20]
D. Zeevi, E. Sharon, M. Lotan-Pompan, Y. Lubling, Z. Shipony, T. Raveh-Sadka, L. Keren, M. Levo, A. Weinberger, and E. Segal, "Compensation for differences in gene copy number among yeast ribosomal proteins is encoded within their promoters," Genome Res., vol. 21, no. 12, pp. 2114--2128, Dec. 2011.
[21]
T. Wasson and A. J. Hartemink, "An ensemble model of competitive multi-factor binding of the genome," Genome Res., vol. 19, no. 11, pp. 2101--12, Nov. 2009.
[22]
A. D. Lander, "The edges of understanding," BMC Biol., vol. 8, p. 40, Jan. 2010.
[23]
H. Kim and E. Gelenbe. (2012). Stochastic gene expression modeling with hill function for switch-like gene responses. IEEE/ACM Trans. Comput. Biol. Bioinformatics {Online}. 9(4), pp. 973--979. Available: http://www.ncbi.nlm.nih.gov/ /22144531
[24]
C. P. Barnes, D. Silk, X. Sheng, and M. P. H. Stumpf, "Bayesian design of synthetic biological systems," Proc. Nat. Acad. Sci. USA, vol. 108, no. 37, pp. 15190--15195, Sep. 2011.
[25]
I. Cantone, L. Marucci, F. Iorio, M. A. Ricci, V. Belcastro, M. Bansal, S. Santini, M. di Bernardo, D. Di Bernardo, and M. P. Cosma. (2009, Apr.). A yeast synthetic network for in vivo assessment of reverse-engineering and modeling approaches. Cell {Online}. 137(1), pp. 172--181. Available: http://www.ncbi.nlm. nih.gov/ /19327819
[26]
A. S. Ribeiro, O. P. Smolander, T. Rajala, A. Häkkinen, and O. Yli-Harja. (2009, Apr.). Delayed stochastic model of transcription at the single nucleotide level. J. Comput. Biol. {Online}. 16(4), pp. 539--553.Available: http://www.ncbi.nlm.nih.gov/ /19361326
[27]
S. Lubliner and E. Segal, "Modeling interactions between adjacent nucleosomes improves genome-wide predictions of nucleosome occupancy," Bioinformatics, vol. 25, no. 12, pp. i348--355, Jun. 2009.
[28]
S. J. Greive, J. P. Goodarzi, S. E. Weitzel, and P. H. von Hippel. (2011, Sep.). Development of a "modular" scheme to describe the kinetics of transcript elongation by RNA polymerase. Biophys. J. {Online}. 101(5), pp. 1155--1165. Available: http://www.ncbi.nlm.nih.gov/ /21889453
[29]
M. R. Roussel and R. Zhu. (2006, Oct.). Stochastic kinetics description of a simple transcription model. Bull. Math. Biol. {Online}. 68(7), pp. 1681--1713. Available: http://www.ncbi.nlm.nih.gov/ /16967259
[30]
M. Levo and E. Segal. (2014, Jul.). In pursuit of design principles of regulatory sequences. Nature Rev. Genetics {Online}. 15(7), pp. 453--68. Available: http://www.ncbi.nlm.nih.gov/ /24913666
[31]
B. Lemon and R. Tjian, "Orchestrated response: A symphony of transcription factors for gene control," Genes Develop., vol. 14, no. 20, pp. 2551--2569, Oct. 2000.
[32]
B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts, and P. Walter, (2007). Molecular Biology of the Cell {Online}. Available: http://www.ncbi.nlm.nih.gov/books/NBK21054/
[33]
G. Badis, M. F. Berger, A. A. Philippakis, S. Talukder, A. R. Gehrke, S. A. Jaeger, E. T. Chan, G. Metzler, A. Vedenko, X. Chen, H. Kuznetsov, C.-f. Wang, D. Coburn, D. E. Newburger, Q. Morris, T. R. Hughes, and M. L. Bulyk, "Diversity and complexity in DNA recognition by transcription factors," Science, vol. 324, no. 5935, pp. 1720--1723, Jun. 2009.
[34]
C. Zhu, K. J. R. P. Byers, R. P. McCord, Z. Shi, M. F. Berger, D. E. Newburger, K. Saulrieta, Z. Smith, M. V. Shah, M. Radhakrishnan, A. A. Philippakis, Y. Hu, F. De Masi, M. Pacek, A. Rolfs, T. Murthy, J. Labaer, and M. L. Bulyk, "High-resolution DNA-bind-ing specificity analysis of yeast transcription factors," Genome Res., vol. 19, no. 4, pp. 556--566, Apr. 2009.
[35]
H. R. Drew and A. A. Travers. (1985, Dec.). DNA bending and its relation to nucleosome positioning. J. Molecular Biol. {Online}. 186(4), pp. 773--90. Available: http://www.ncbi.nlm.nih.gov/ /3912515
[36]
A. V. Morozov, K. Fortney, D. A. Gaykalova, V. M. Studitsky, J. Widom, and E. D. Siggia, "Using DNA mechanics to predict in vitro nucleosome positions and formation energies," Nucleic Acids Res., vol. 37, no. 14, pp. 4707--4722, Aug. 2009.
[37]
P. T. Lowary and J. Widom. (1998, Feb.). New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning. J. Molecular Biol. {Online}. 276(1), pp. 19--42. Available: http://www.ncbi.nlm.nih.gov/ /9514715
[38]
H. S. Rhee and B. F. Pugh, "Genome-wide structure and organization of eukaryotic pre-initiation complexes," Nature, vol. 487, no. 7389, pp. 128--128, Mar. 2012.
[39]
K. D. MacIsaac and E. Fraenkel, "Practical strategies for discovering regulatory DNA sequence motifs," PLoS Comput. Biol., vol. 2, no. 4, pp. 201--210, Apr. 2006.
[40]
A. M. Sengupta, M. Djordjevic, and B. I. Shraiman, "Specificity and robustness in transcription control networks," Proc. Nat. Acad. Sci. USA, vol. 99, no. 4, pp. 2072--2077, Feb. 2002.
[41]
O. G. Berg, R. B. Winter, and P. H. von Hippel. (1981, Nov.). Diffusion-driven mechanisms of protein translocation on nucleic acids. 1. Models and theory. Biochemistry {Online}. 20(24), pp. 6929--6948. Available: http://www.ncbi.nlm.nih.gov/ /7317363
[42]
J. L. Workman. (2006, Aug.). Nucleosome displacement in transcription. Genes Develop. {Online}. 20(15), pp. 2009--2017. Available: http://www.ncbi.nlm.nih.gov/ /16882978
[43]
O. I. Kulaeva, F.-K. Hsieh, H.-W. Chang, D. S. Luse, and V. M. Studitsky. (2013, Jan.). Mechanism of transcription through a nucleo-some by RNA polymerase II. Biochimica et Biophysica Acta {Online}. 1829(1), pp. 76--83. Available: http://www.ncbi.nlm.nih.gov/ /22982194
[44]
A. Coulon, C. C. Chow, R. H. Singer, and D. R. Larson. (2013, Aug.). Eukaryotic transcriptional dynamics: From single molecules to cell populations. Nature Rev. Genetics {Online}. 14(8), pp. 572--584. Available: http://www.nature.com/doifinder/10.1038/nrg3484
[45]
E. M. Prescott and N. J. Proudfoot, "Transcriptional collision between convergent genes in budding yeast," Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 13, pp. 8796--8801, Jun. 2002.
[46]
C. F. Hongay, P. L. Grisafi, T. Galitski, and G. R. Fink, "Antisense transcription controls cell fate in Saccharomyces cerevisiae," Cell, vol. 127, no. 4, pp. 735--45, Nov. 2006. {Online}. Available: http://www.ncbi.nlm.nih.gov/ /17110333
[47]
S. L. Bumgarner, R. D. Dowell, P. Grisafi, D. K. Gifford, and G. R. Fink, "Toggle involving cis-interfering noncoding RNAs controls variegated gene expression in yeast," Proc. Nat. Acad. Sci. USA, vol. 106, no. 43, pp. 18321--18326, Oct. 2009.
[48]
P. Thebault, G. Boutin, W. Bhat, A. Rufiange, J. Martens, and A. Nourani. (2011, Mar.). Transcription regulation by the noncoding RNA SRG1 requires Spt2-dependent chromatin deposition in the wake of RNA polymerase II. Molecular Cellular Biol. {Online}. 31(6), pp. 1288--1300. Available: http://www.ncbi.nlm.nih.gov/ /21220514
[49]
S. J. Hainer, J. A. Pruneski, R. D. Mitchell, R. M. Monteverde, and J. A. Martens, "Intergenic transcription causes repression by directing nucleosome assembly," Genes Develop., vol. 25, no. 1, pp. 29--40, Jan. 2011.
[50]
V. Pelechano, S. Chavez, and J. E. Perez-Ort?n, "A complete set of nascent transcription rates for yeast genes," PloS One, vol. 5, no. 11, p. e15442, Jan. 2010.
[51]
M. B. Elowitz, A. J. Levine, E. D. Siggia, and P. S. Swain. (2002, Aug.). Stochastic gene expression in a single cell. Science {Online}. 297(5584), pp. 1183--1186. Available: http://www.ncbi.nlm.nih.gov/ /12183631
[52]
B. B. Kaufmann and A. van Oudenaarden. (2007, Apr.). Stochastic gene expression: From single molecules to the proteome. Current Opinion Genetics Develop. {Online}. 17(2), pp. 107--112. Available: http://www.ncbi.nlm.nih.gov/ /17317149
[53]
S. Huang, "Non-genetic heterogeneity of cells in development: more than just noise," Development, vol. 136, no. 23, pp. 3853--3862, Dec. 2009.
[54]
A. Schwabe, M. Dobrzyski, K. Rybakova, P. Verschure, and F. J. Bruggeman. (2011, Jan.). Origins of stochastic intracellular processes and consequences for cell-to-cell variability and cellular survival strategies," Methods Enzymol. {Online}. 500, pp. 597--625. Available: http://www.ncbi.nlm.nih.gov/ /21943916
[55]
N. Tenazinha and S. Vinga. (2011). A survey on methods for modeling and analyzing integrated biological networks. IEEE/ACM Trans. Comput. Biol. Bioinf. {Online}. 8(4), pp. 943--958. Available: http://www.ncbi.nlm.nih.gov/ /21116043
[56]
G. Karlebach and R. Shamir. (2008, Oct.). Modelling and analysis of gene regulatory networks. Nature Rev. Molecular Cell Biol. {Online}. 9(10), pp. 770--780. Available: http://www.ncbi.nlm.nih.gov/ /18797474
[57]
A. Ay and D. N. Arnosti, "Mathematical modeling of gene expression: A guide for the perplexed biologist," Critical Rev. Biochem. Molecular Biol., vol. 46, no. 2, pp. 137--151, Apr. 2011.
[58]
M. Hecker, S. Lambeck, S. Toepfer, E. van Someren, and R. Guthke. (2009, Apr.). Gene regulatory network inference: Data integration in dynamic models-a review. Bio Syst. {Online}. 96(1), pp. 86--103. Available: http://www.ncbi.nlm.nih.gov/ /19150482
[59]
M. Karplus and J. A. McCammon. (2002, Sep.). Molecular dynamics simulations of biomolecules. Nature Structural Biol., vol. 9, no. 9, pp. 646--52, Sep. 2002. {Online}. Available: http://www.ncbi.nlm.nih.gov/ /12198485
[60]
A. S. Ribeiro. (2010, Jan.). Stochastic and delayed stochastic models of gene expression and regulation. Math. Biosci. {Online}. 223 (1), pp. 1--11. Available: http://www.ncbi.nlm.nih.gov/ /19883665
[61]
C. Chaouiya. (2007, Jul.). Petri net modelling of biological networks. Briefings Bioinf. {Online}. 8(4), pp. 210--219. Available: http://www.ncbi.nlm.nih.gov/ /17626066
[62]
A. Sanchez, S. Choubey, and J. Kondev. (2013, Jul.). Stochastic models of transcription: From single molecules to single cells. Methods {Online}. 62(1), pp. 13--25. Available: http://www.ncbi. nlm.nih.gov/ /23557991
[63]
D. T. Gillespie. (1976, Dec). A general method for numerically simulating the stochastic time evolution of coupled chemical reactions. J. Comput. Phys. {Online}. 22(4), pp. 403--434. Available: http://linkinghub.elsevier.com/retrieve/pii/0021999176900413
[64]
A. J. Black and A. J. McKane. (2012, Jun.). Stochastic formulation of ecological models and their applications. Trends Ecol. Evol., vol. 27, no. 6, pp. 337--45, Jun. 2012. {Online}. Available: http://www.ncbi.nlm.nih.gov/ /22406194
[65]
K. Takahashi, K. Kaizu, B. Hu, and M. Tomita. (2004, Mar.). A multi-algorithm, multi-timescale method for cell simulation. Bio-informatics {Online}. 20(4), pp. 538--546. Available: http://www.ncbi.nlm.nih.gov/ /14990450
[66]
K. Sneppen, I. B. Dodd, K. E. Shearwin, A. C. Palmer, R. A. Schubert, B. P. Callen, and J. B. Egan. (2005, Feb.). A mathematical model for transcriptional interference by RNA polymerase traffic in Escherichia coli. J. Molecular Biol. {Online}. 346(2), pp. 399--409. Available: http://www.ncbi.nlm.nih.gov/ /15670592
[67]
T. D. Schneider and R. M. Stephens, "Sequence logos: A new way to display consensus sequences," Nucleic Acids Res., vol. 18, no. 20, pp. 6097--6100, Oct. 1990.
[68]
M. L. Kireeva, B. Hancock, G. H. Cremona, W. Walter, V. M. Studitsky, and M. Kashlev. (2005, Apr.). Nature of the nucleosomal barrier to RNA polymerase II. Molecular Cell {Online}. 18(1), pp. 97--108. Available: http://www.ncbi.nlm.nih.gov/ /15808512
[69]
J. Mäkelä, J. Lloyd-Price, O. Yli-Harja, and A. S. Ribeiro, "Stochastic sequence-level model of coupled transcription and translation in prokaryotes," BMC Bioinf., vol. 12, no. 1, p. 121, Jan. 2011.
[70]
R. Zhu, A. S. Ribeiro, D. Salahub, and S. A. Kauffman. (2007, Jun.). Studying genetic regulatory networks at the molecular level: Delayed reaction stochastic models. J. Theoretical Biol. {Online}. 246(4), pp. 725--745. Available: http://www.ncbi.nlm.nih.gov/ /17350653
[71]
M. J. Schilstra and C. L. Nehaniv. (2010, Oct.). Stochastic model of template-directed elongation processes in biology. Bio Syst. {Online}. 102(1), pp. 55--60. Available: http://www.ncbi.nlm.nih.gov/ /20655359
[72]
H. Genrich, R. Kuffner, and K. Voss, "Executable Petri net models for the analysis of metabolic pathways," Int. J. STTT, vol. 3, pp. 394--404, 2001.
[73]
D. Ruths, M. Muller, J.-T. Tseng, L. Nakhleh, and P. T. Ram, "The signaling petri net-based simulator: a non-parametric strategy for characterizing the dynamics of cell-specific signaling networks," PLoS Comput. Biol., vol. 4, no. 2, p. e1000005, Feb. 2008.
[74]
I. Mura and A. Csik´sz-Nagy. (2008, Oct.). Stochastic petri net extension of a yeast cell cycle model. J. Theoretical Biol. {Online}. 254(4), pp. 850--860. Available: http://www.ncbi.nlm.nih.gov/ /18703074
[75]
J. Lei. (2011). A modular, qualitative modeling of regulatory networks using petri nets. Modeling Syst. Biol. {Online}. 16(25). Available: http://www.springerlink.com/index/10.1007/978-1-84996-474-6_12
[76]
S. F. Tolić-Nørrelykke, A. M. Engh, R. Landick, and J. Gelles. (2004, Jan.). Diversity in the rates of transcript elongation by single RNA polymerase molecules, The J. Biol. Chem. {Online}. 279(5), pp. 3292--3299. Available: http://www.ncbi.nlm.nih.gov/ /14604986
[77]
G. O. Bryant and M. Ptashne. (2003, May). Independent recruitment in vivo by Gal4 of two complexes required for transcription. Molecular Cell {Online}. 11(5), pp. 1301--1309. Available: http://www.ncbi.nlm.nih.gov/ /12769853
[78]
M. A. Schwabish and K. Struhl, "Evidence for eviction and rapid deposition of histones upon transcriptional elongation by RNA polymerase II," Molecular Cellular Biol., vol. 24, no. 23, pp. 10111--10117, Dec. 2004.
[79]
M. Gullerova and N. J. Proudfoot. (2010, Jan.). Transcriptional interference and gene orientation in yeast: Noncoding RNA connections. Cold Spring Harbor Symposia Quantitative Biol. {Online}. 75, pp. 299--311. Available: http://www.ncbi.nlm.nih.gov/ /21467144
[80]
S. Ghaemmaghami, W.-K. Huh, K. Bower, R. W. Howson, A. Belle, N. Dephoure, E. K. O'Shea, and J. S. Weissman. (2003, Oct.). Global analysis of protein expression in yeast. Nature {Online}. 425(6959), pp. 737--741. Available: http://www.ncbi.nlm.nih.gov/ /14562106
[81]
K. D. MacIsaac, T. Wang, D. B. Gordon, D. K. Gifford, G. D. Stormo, and E. Fraenkel, "An improved map of conserved regulatory sites for Saccharomyces cerevisiae," BMC Bioinf., vol. 7, p. 113, Jan. 2006.
[82]
N. Kaplan, I. K. Moore, Y. Fondufe-Mittendorf, A. J. Gossett, D. Tillo, Y. Field, E. M. LeProust, T. R. Hughes, J. D. Lieb, J. Widom, and E. Segal, "The DNA-encoded nucleosome organization of a eukaryotic genome," Nature, vol. 458, no. 7236, pp. 362--366, Mar. 2009.
[83]
J. D. Lieb, X. Liu, D. Botstein, and P. O. Brown. (2011, Aug.). Promoter-specific binding of Rap1 revealed by genome-wide maps of protein-DNA association. Nature Genetics {Online}. 28(4), pp. 327--334. Available: http://www.ncbi.nlm.nih.gov/ /11455386
[84]
S. Ramsey, D. Orrell, and H. Bolouri. (2005, May). Dizzy: Stochastic simulation of large-scale genetic regulatory networks. J. Bioinf. Comput. Biol. {Online}. 3(2), pp. 415--436. Available: http://www.ncbi.nlm.nih.gov/ /15852513
[85]
M. A. Gibson and J. Bruck, "Efficient exact stochastic simulation of chemical systems with many species and many channels," The J. Phys. Chem. A, vol. 104, no. 9, pp. 1876--1889, Mar. 2000.
[86]
Y. Qi, A. Rolfe, K. D. MacIsaac, G. K. Gerber, D. Pokholok, J. Zeitlinger, T. Danford, R. D. Dowell, E. Fraenkel, T. S. Jaakkola, R. A. Young, and D. K. Gifford. (2006, Aug.). High-resolution computational models of genome binding events. Nature Biotechnol. {Online}. 24(8), pp. 963--970. Available: http://www.ncbi.nlm.nih.gov/ /16900145
[87]
F. Erhard, C. C. Friedel, and R. Zimmer, "FERN-a Java framework for stochastic simulation and evaluation of reaction networks," BMC Bioinf., vol. 9, p. 356, Jan. 2008.
[88]
M. W. Sneddon, J. R. Faeder, and T. Emonet, "Efficient modeling, simulation and coarse-graining of biological complexity with NFsim," Nature Methods, vol. 8, no. 2, pp. 177--183, 2011.
[89]
J. Colvin, M. I. Monine, J. R. Faeder, W. S. Hlavacek, D. D. Von Hoff, and R. G. Posner. (2009, Apr.). Simulation of large-scale rule-based models. Bioinformatics {Online}. 25(7), pp. 910--917 Available: http://www.ncbi.nlm.nih.gov/ /19213740
[90]
W. Lee, D. Tillo, N. Bray, R. H. Morse, R. W. Davis, T. R. Hughes, and C. Nislow. (2007, Oct.). A high-resolution atlas of nucleosome occupancy in yeast. Nature Genetics {Online}. 39(10), pp. 1235--1244. Available: http://www.ncbi.nlm.nih.gov/ /17873876
[91]
A. Jansen, E. van der Zande, W. Meert, G. R. Fink, and K. J. Verstrepen, "Distal chromatin structure influences local nucleosome positions and gene expression," Nucleic Acids Res., vol. 40, no. 9, pp. 3870--85, May 2012.
[92]
B. Gelfand, J. Mead, A. Bruning, N. Apostolopoulos, V. Tadigotla, V. Nagaraj, A. M. Sengupta, and A. K. Vershon, "Regulated anti-sense transcription controls expression of cell-type-specific genes in yeast," Molecular Cellular Biol., vol. 31, no. 8, pp. 1701--1709, Apr. 2011.
[93]
M. F. Dion, T. Kaplan, M. Kim, S. Buratowski, N. Friedman, and O. J. Rando. (2007, Mar.). Dynamics of replication-independent histone turnover in budding yeast. Science {Online}. 315(5817), pp. 1405--1408. Available: http://www.ncbi.nlm.nih.gov/ /17347438
[94]
A. J. Andrews and K. Luger. (2011, Jan.). Nucleosome structure(s) and stability: Variations on a theme. Ann. Rev. Biophys. {Online}. 40, pp. 99--117. Available: http://www.ncbi.nlm.nih.gov/ /21332355
[95]
G. Li, M. Levitus, C. Bustamante, and J. Widom. (2005, Jan.). Rapid spontaneous accessibility of nucleosomal DNA. Nature Structural Molecular Biol. {Online}. 12(1), pp. 46--53. Available: http://www.ncbi.nlm.nih.gov/ /15580276
[96]
V. Böhm, A. R. Hieb, A. J. Andrews, A. Gansen, A. Rocker, K. Tòth, K. Luger, and J. Langowski, "Nucleosome accessibility governed by the dimer/tetramer interface," Nucleic Acids Res., vol. 39, no. 8, pp. 3093--3102, Apr. 2011.
[97]
S. L. Berger, "Histone modifications in transcriptional regulation," Current Opinion Genetics Develop., vol. 12, pp. 142--148, 2002.
[98]
J. Pahle, "Biochemical simulations: Stochastic, approximate stochastic and hybrid approaches," Briefings Bioinf., vol. 10, no. 1, pp. 53--64, Jan. 2009.
- A modeling framework for generation of positional and temporal simulations of transcriptional regulation
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IEEE Computer Society Press
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Published: 01 May 2016
Published in TCBB Volume 13, Issue 3
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