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Cited by 44Genomics and Chromatin DynamicsGene Regulatory Network AnalysisDevelopmental Biology and Gene Regulation

Dynamic CRM occupancy reflects a temporal map of developmental progression

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Wilczyński, Bartek, Furlong, Eileen E M·2010·Molecular Systems Biology
DOI 10.1038/msb.2010.35PMC PMC2913398
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Abstract

Development is driven by tightly coordinated spatio-temporal patterns of gene expression, which are initiated through the action of transcription factors (TFs) binding to cis-regulatory modules (CRMs). Although many studies have investigated how spatial patterns arise, precise temporal control of gene expression is less well understood. Here, we show that dynamic changes in the timing of CRM occupancy is a prevalent feature common to all TFs examined in a developmental ChIP time course to date. CRMs exhibit complex binding patterns that cannot be explained by the sequence motifs or expression of the TFs themselves. The temporal changes in TF binding are highly correlated with dynamic patterns of target gene expression, which in turn reflect transitions in cellular function during different stages of development. Thus, it is not only the timing of a TF's expression, but also its temporal occupancy in refined time windows, which determines temporal gene expression. Systematic measurement of dynamic CRM occupancy may therefore serve as a powerful method to decode dynamic changes in gene expression driving developmental progression.

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  • Transcription factor binding to DNA appears to be very transient.

    “While it is clear that enhancers typically favour the more flexible models of sequence organisation, the degree of necessary cooperation between TFs is less obvious, particularly since TF binding to DNA appears to be very transient [113–117].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [113]

    The Results and discussion report that each of four transcription factors occupies about 50% of its targeted regulatory modules transiently during Drosophila development. This supports changing DNA occupancy over developmental stages, but not the broader implication that transcription-factor binding to DNA is generally short-lived at the molecular level. (LLM, conf=0.86)

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Research works printed but not linked: 53

  1. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G (2000) Gene Ontology: tool for the unification of biology. Nat Genet 25: 25– 29 10802651 PMC3037419
  2. Azpiazu N, Frasch M (1993) Tinman and bagpipe: two homeo box genes that determine cell fates in the dorsal mesoderm of Drosophila. Genes Dev 7: 1325– 1340 8101173
  3. Bolstad BM, Irizarry RA, Astrand M, Speed TP (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19: 185– 193 12538238
  4. Bour BA, O'Brien MA, Lockwood WL, Goldstein ES, Bodmer R, Taghert PH, Abmayr SM, Nguyen HT (1995) Drosophila MEF2, a transcription factor that is essential for myogenesis. Genes Dev 9: 730– 741 7729689
  5. Broadus J, McCabe JR, Endrizzi B, Thummel CS, Woodard CT (1999) The Drosophila beta FTZ-F1 orphan nuclear receptor provides competence for stage-specific responses to the steroid hormone ecdysone. Mol Cell 3: 143– 149 10078197
  6. Bruneau BG, Logan M, Davis N, Levi T, Tabin CJ, Seidman JG, Seidman CE (1999) Chamber-specific cardiac expression of Tbx5 and heart defects in Holt-Oram syndrome. Dev Biol 211: 100– 108 10373308
  7. Buck MJ, Lieb JD (2006) A chromatin-mediated mechanism for specification of conditional transcription factor targets. Nat Genet 38: 1446– 1451 17099712 PMC2756100
  8. Chen X, Xu H, Yuan P, Fang F, Huss M, Vega VB, Wong E, Orlov YL, Zhang W, Jiang J, Loh Y-H, Yeo HC, Yeo ZX, Narang V, Govindarajan KR, Leong B, Shahab A, Ruan Y, Bourque G, Sung W-K (2008) Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133: 1106– 1117 18555785
  9. Cock PJA, Antao T, Chang JT, Chapman BA, Cox CJ, Dalke A, Friedberg I, Hamelryck T, Kauff F, Wilczynski B, de Hoon MJL (2009) Biopython: freely available Python tools for computational molecular biology and bioinformatics. Bioinformatics 25: 1422– 1423 19304878 PMC2682512
  10. Das D, Nahle Z, Zhang MQ (2006) Adaptively inferring human transcriptional subnetworks. Mol Syst Biol 2: 2006 0029 16760900 PMC1681499
  11. de Hoon MJ, Imoto S, Nolan J, Miyano S (2004) Open source clustering software. Bioinformatics 20: 1453– 1454 14871861
  12. Down TA, Bergman CM, Su J, Hubbard TJP (2007) Large-scale discovery of promoter motifs in Drosophila melanogaster. PLoS Comput Biol 3: e7 17238282 PMC1779301
  13. Duan H, Skeath JB, Nguyen HT (2001) Drosophila Lame duck, a novel member of the Gli superfamily, acts as a key regulator of myogenesis by controlling fusion-competent myoblast development. Development 128: 4489– 4500 11714674
  14. Gao F, Foat BC, Bussemaker HJ (2004) Defining transcriptional networks through integrative modeling of mRNA expression and transcription factor binding data. BMC Bioinformatics 5: 31 15113405 PMC407845
  15. Gaudet J, Mango SE (2002) Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4. Science 295: 821– 825 11823633
  16. Gaudet J, Muttumu S, Horner M, Mango SE (2004) Whole-genome analysis of temporal gene expression during foregut development. PLoS Biol 2: e352 15492775 PMC523228
  17. Goldman TD, Arbeitman MN (2007) Genomic and functional studies of Drosophila sex hierarchy regulated gene expression in adult head and nervous system tissues. PLoS Genet 3: e216 18039034 PMC2082469
  18. Grossmann S, Bauer S, Robinson PN, Vingron M (2007) Improved detection of overrepresentation of Gene-Ontology annotations with parent child analysis. Bioinformatics 23: 3024– 3031 17848398
  19. Halfon MS, Carmena A, Gisselbrecht S, Sackerson CM, Jimenez F, Baylies MK, Michelson AM (2000) Ras pathway specificity is determined by the integration of multiple signal-activated and tissue-restricted transcription factors. Cell 103: 63– 74 11051548
  20. Harbison CT, Gordon DB, Lee TI, Rinaldi NJ, Macisaac KD, Danford TW, Hannett NM, Tagne J-B, Reynolds DB, Yoo J, Jennings EG, Zeitlinger J, Pokholok DK, Kellis M, Rolfe PA, Takusagawa KT, Lander ES, Gifford DK, Fraenkel E, Young RA (2004) Transcriptional regulatory code of a eukaryotic genome. Nature 431: 99– 104 15343339 PMC3006441
  21. Hertz GZ, Stormo GD (1999) Identifying DNA and protein patterns with statistically significant alignments of multiple sequences. Bioinformatics 15: 563– 577 10487864
  22. Ip YT, Park RE, Kosman D, Yazdanbakhsh K, Levine M (1992) Dorsal-twist interactions establish snail expression in the presumptive mesoderm of the Drosophila embryo. Genes Dev 6: 1518– 1530 1644293
  23. Jakobsen JS, Braun M, Astorga J, Gustafson EH, Sandmann T, Karzynski M, Carlsson P, Furlong EEM (2007) Temporal ChIP-on-chip reveals Biniou as a universal regulator of the visceral muscle transcriptional network. Genes Dev 21: 2448 17908931 PMC1993875
  24. Jothi R, Balaji S, Wuster A, Grochow JA, Gsponer J, Przytycka TM, Aravind L, Babu MM (2009) Genomic analysis reveals a tight link between transcription factor dynamics and regulatory network architecture. Mol Syst Biol 5: 294 19690563 PMC2736650
  25. Krejci A, Bernard F, Housden BE, Collins S, Bray SJ (2009) Direct response to Notch activation: signaling crosstalk and incoherent logic. Sci Signal 2: ra1 19176515
  26. Lagha M, Kormish JD, Rocancourt D, Manceau M, Epstein JA, Zaret KS, Relaix F, Buckingham ME (2008) Pax3 regulation of FGF signaling affects the progression of embryonic progenitor cells into the myogenic program. Genes Dev 22: 1828– 1837 18593883 PMC2492669
  27. Lee HH, Frasch M (2005) Nuclear integration of positive Dpp signals, antagonistic Wg inputs and mesodermal competence factors during Drosophila visceral mesoderm induction. Development 132: 1429– 1442 15750188
  28. Lee TI, Rinaldi NJ, Robert F, Odom DT, Bar-Joseph Z, Gerber GK, Hannett NM, Harbison CT, Thompson CM, Simon I, Zeitlinger J, Jennings EG, Murray HL, Gordon DB, Ren B, Wyrick JJ, Tagne J-B, Volkert TL, Fraenkel E, Gifford DK (2002) Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 298: 799– 804 12399584
  29. Leptin M (1991) twist and snail as positive and negative regulators during Drosophila mesoderm development. Genes Dev 5: 1568– 1576 1884999
  30. Li C, Kapitskaya MZ, Zhu J, Miura K, Segraves W, Raikhel AS (2000) Conserved molecular mechanism for the stage specificity of the mosquito vitellogenic response to ecdysone. Dev Biol 224: 96– 110 10898964
  31. Li L, Zhu Q, He X, Sinha S, Halfon M (2007) Large-scale analysis of transcriptional cis-regulatory modules reveals both common features and distinct subclasses. Genome Biol 8: R101 17550599 PMC2394749
  32. Li X-Y, MacArthur S, Bourgon R, Nix D, Pollard DA, Iyer VN, Hechmer A, Simirenko L, Stapleton M, Hendriks CLL, Chu HC, Ogawa N, Inwood W, Sementchenko V, Beaton A, Weiszmann R, Celniker SE, Knowles DW, Gingeras T, Speed TP (2008) Transcription factors bind thousands of active and inactive regions in the Drosophila blastoderm. PLoS Biol 6: e27 EP 18271625 PMC2235902
  33. Lilly B, Galewsky S, Firulli AB, Schulz RA, Olson EN (1994) D-MEF2: a MADS box transcription factor expressed in differentiating mesoderm and muscle cell lineages during Drosophila embryogenesis. Proc Natl Acad Sci USA 91: 5662– 5666 8202544 PMC44056
  34. Lin Q, Schwarz J, Bucana C, Olson EN (1997) Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C. Science 276: 1404– 1407 9162005 PMC4437729
  35. Liu Y-H, Jakobsen JS, Valentin G, Amarantos I, Gilmour DT, Furlong EEM (2009) A systematic analysis of tinman function reveals Eya and JAK-STAT signaling as essential regulators of muscle development. Dev Cell 16: 280– 291 19217429
  36. Luscombe NM, Madan Babu M, Yu H, Snyder M, Teichmann SA, Gerstein M (2004) Genomic analysis of regulatory network dynamics reveals large topological changes. Nature 431: 308– 312 15372033
  37. MacArthur S, Li X-Y, Li J, Brown J, Chu HC, Zeng L, Grondona B, Hechmer A, Simirenko L, Keranen S, Knowles D, Stapleton M, Bickel P, Biggin M, Eisen M (2009) Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions. Genome Biol 10: R80 19627575 PMC2728534
  38. Morley RH, Lachani K, Keefe D, Gilchrist MJ, Flicek P, Smith JC, Wardle FC (2009) A gene regulatory network directed by zebrafish No tail accounts for its roles in mesoderm formation. Proc Natl Acad Sci USA 106: 3829– 3834 19225104 PMC2656165
  39. Nguyen HT, Bodmer R, Abmayr SM, McDermott JC, Spoerel NA (1994) D-mef2: a Drosophila mesoderm-specific MADS box-containing gene with a biphasic expression profile during embryogenesis. Proc Natl Acad Sci USA 91: 7520– 7524 8052612 PMC44433
  40. Ni L, Bruce C, Hart C, Leigh-Bell J, Gelperin D, Umansky L, Gerstein MB, Snyder M (2009) Dynamic and complex transcription factor binding during an inducible response in yeast. Genes Dev 23: 1351– 1363 19487574 PMC2701586
  41. Roider HG, Kanhere A, Manke T, Vingron M (2007) Predicting transcription factor affinities to DNA from a biophysical model. Bioinformatics 23: 134– 141 17098775
  42. Sandelin A, Alkema W, Engstrom P, Wasserman WW, Lenhard B (2004) JASPAR: an open-access database for eukaryotic transcription factor binding profiles. Nucl Acids Res 32: D91– D94 14681366 PMC308747
  43. Sandmann T, Jensen LJ, Jakobsen JS, Karzynski MM, Eichenlaub MP, Bork P, Furlong EEM (2006) A temporal map of transcription factor activity: Mef2 directly regulates target genes at all stages of muscle development. Dev Cell 10: 797– 807 16740481
  44. Suzuki H, Forrest AR, van Nimwegen E, Daub CO, Balwierz PJ, Irvine KM, Lassmann T, Ravasi T, Hasegawa Y, de Hoon MJ, Katayama S, Schroder K, Carninci P, Tomaru Y, Kanamori-Katayama M, Kubosaki A, Akalin A, Ando Y, Arner E, Asada M (2009) The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line. Nat Genet 41: 553– 562 19377474 PMC6711855
  45. Thisse B, el Messal M, Perrin-Schmitt F (1987) The twist gene: isolation of a Drosophila zygotic gene necessary for the establishment of dorsoventral pattern. Nucleic Acids Res 15: 3439– 3453 3106932 PMC340740
  46. Tomancak P, Beaton A, Weiszmann R, Kwan E, Shu S, Lewis SE, Richards S, Ashburner M, Hartenstein V, Celniker SE, Rubin GM (2002) Systematic determination of patterns of gene expression during Drosophila embryogenesis. Genome Biol 3: RESEARCH0088 12537577 PMC151190
  47. Ucar D, Beyer A, Parthasarathy S, Workman CT (2009) Predicting functionality of protein-DNA interactions by integrating diverse evidence. Bioinformatics 25: i137– i144 19477979 PMC2687967
  48. Vokes SA, Ji H, Wong WH, McMahon AP (2008) A genome-scale analysis of the cis-regulatory circuitry underlying sonic hedgehog-mediated patterning of the mammalian limb. Genes Dev 22: 2651– 2663 18832070 PMC2559910
  49. Wilczyński B, Hvidsten TR, Kryshtafovych A, Tiuryn J, Komorowski J, Fidelis K (2006) Using local gene expression similarities to discover regulatory binding site modules. BMC Bioinformatics 7: 505 17109764 PMC2001304
  50. Woodard CT, Baehrecke EH, Thummel CS (1994) A molecular mechanism for the stage specificity of the Drosophila prepupal genetic response to ecdysone. Cell 79: 607– 615 7954827
  51. Zaffran S, Kuchler A, Lee HH, Frasch M (2001) biniou (FoxF), a central component in a regulatory network controlling visceral mesoderm development and midgut morphogenesis in Drosophila. Genes Dev 15: 2900– 2915 11691840 PMC312807
  52. Zeitlinger J, Zinzen RP, Stark A, Kellis M, Zhang H, Young RA, Levine M (2007) Whole-genome ChIP–chip analysis of dorsal, twist, and snail suggests integration of diverse patterning processes in the Drosophila embryo. Genes Dev 21: 385 17322397 PMC1804326
  53. Zinzen RP, Girardot C, Gagneur J, Braun M, Furlong EEM (2009) Combinatorial transcription factor binding predicts spatio-temporal cis-regulatory activity. Nature 462: 65– 70 19890324

Cited by

Sorted by citations

Authors
Wilczyński, B., & Furlong, E. E. M.
Affiliations
European Molecular Biology Laboratory (DE)
Corresponding author
Furlong, Eileen E M
ORCID
Venue
Molecular Systems Biology
Publisher
Springer Science and Business Media LLC
Published
2010-06-22
Volume
6
Issue
1
Pages
383-383
ISSN
1744-4292 (ISSN-L)
DOI
10.1038/msb.2010.35
PMC
PMC2913398
OpenAlex
W2103941911
Cited by
44
References
2
Citations by year
2024: 1 · 2023: 1 · 2021: 5 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 1 · 2014: 2 · 2013: 7 · 2012: 10
FWCI
3.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Systems Biology (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
cis-regulatory modules, transcription factor binding, temporal gene expression, developmental gene regulation, target gene expression, cis-regulatory motifs, developmental transitions
MeSH terms
Animals, Drosophila melanogaster, Protein Binding, Regulatory Sequences, Nucleic Acid, Time Factors, Transcription Factors, Gene Expression Regulation, Developmental, Drosophila Proteins

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