Cis-Regulatory Mechanisms for Robust Olfactory Sensory Neuron Class-restricted Odorant Receptor Gene Expression in

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Our neurons can become over a hundred years old. Even if neurons are restructured and remodeled by their constant work of receiving, storing and sending information, they stay devoted to one single task and retain their identity for their whole life. How a neuron keeps its identity is not well understood. In the olfactory system, the identity of the olfactory sensory neuron (OSN) is a result of the expression of a single odorant receptor (OR) from a large receptor gene repertoire in the genome. Neurons that share an expressed receptor make a functional class. Here, we identify clusters of transcription factor binding motifs to be the smallest unit that drive expression in a single olfactory sensory neuron class. We further demonstrate that it is the structure of the cluster that determines the class specific expression. However, environmental stress, such as temperature changes or starvation, destabilizes the expression produced by the cluster. Our results demonstrate that stable expression is generated from redundant motifs outside the cluster and suggest that cooperative regulation generates robust expression of the genes that determine neuronal identity and function.

Vyšlo v časopise: Cis-Regulatory Mechanisms for Robust Olfactory Sensory Neuron Class-restricted Odorant Receptor Gene Expression in. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005051
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005051

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Zdroje

1. Lagha M, Bothma JP, Levine M (2012) Mechanisms of transcriptional precision in animal development. Trends Genet 28: 409–416. doi: 10.1016/j.tig.2012.03.006 22513408

2. Frankel N, Davis GK, Vargas D, Wang S, Payre F, et al. (2010) Phenotypic robustness conferred by apparently redundant transcriptional enhancers. Nature 466: 490–493. doi: 10.1038/nature09158 20512118

3. Ebert MS, Sharp PA (2010) Emerging roles for natural microRNA sponges. Curr Biol 20: R858–861. doi: 10.1016/j.cub.2010.08.052 20937476

4. Couto A, Alenius M, Dickson BJ (2005) Molecular, anatomical, and functional organization of the Drosophila olfactory system. Curr Biol 15: 1535–1547. 16139208

5. Fishilevich E, Vosshall LB (2005) Genetic and functional subdivision of the Drosophila antennal lobe. Curr Biol 15: 1548–1553. 16139209

6. Fuss SH, Ray A (2009) Mechanisms of odorant receptor gene choice in Drosophila and vertebrates. Mol Cell Neurosci 41: 101–112. doi: 10.1016/j.mcn.2009.02.014 19303443

7. Tharadra SK, Medina A, Ray A (2013) Advantage of the Highly Restricted Odorant Receptor Expression Pattern in Chemosensory Neurons of. PLoS One 8: e66173. 23840419

8. Buck L, Axel R (1991) A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 65: 175–187. 1840504

9. Vosshall LB, Amrein H, Morozov PS, Rzhetsky A, Axel R (1999) A spatial map of olfactory receptor expression in the Drosophila antenna. Cell 96: 725–736. 10089887

10. Wang SS, Tsai RY, Reed RR (1997) The characterization of the Olf-1/EBF-like HLH transcription factor family: implications in olfactory gene regulation and neuronal development. J Neurosci 17: 4149–4158. 9151732

11. Hirota J, Mombaerts P (2004) The LIM-homeodomain protein Lhx2 is required for complete development of mouse olfactory sensory neurons. Proc Natl Acad Sci U S A 101: 8751–8755. 15173589

12. Kolterud A, Alenius M, Carlsson L, Bohm S (2004) The Lim homeobox gene Lhx2 is required for olfactory sensory neuron identity. Development 131: 5319–5326. 15456728

13. McIntyre JC, Bose SC, Stromberg AJ, McClintock TS (2008) Emx2 stimulates odorant receptor gene expression. Chem Senses 33: 825–837. doi: 10.1093/chemse/bjn061 18854508

14. Tichy AL, Ray A, Carlson JR (2008) A new Drosophila POU gene, pdm3, acts in odor receptor expression and axon targeting of olfactory neurons. J Neurosci 28: 7121–7129. doi: 10.1523/JNEUROSCI.2063-08.2008 18614681

15. Bai L, Carlson JR (2010) Distinct functions of acj6 splice forms in odor receptor gene choice. J Neurosci 30: 5028–5036. doi: 10.1523/JNEUROSCI.6292-09.2010 20371823

16. Jafari S, Alkhori L, Schleiffer A, Brochtrup A, Hummel T, et al. (2012) Combinatorial activation and repression by seven transcription factors specify Drosophila odorant receptor expression. PLoS Biol 10: e1001280. doi: 10.1371/journal.pbio.1001280 22427741

17. Sim CK, Perry S, Tharadra SK, Lipsick JS, Ray A (2012) Epigenetic regulation of olfactory receptor gene expression by the Myb-MuvB/dREAM complex. Genes Dev 26: 2483–2498. doi: 10.1101/gad.201665.112 23105004

18. Vassalli A, Feinstein P, Mombaerts P (2011) Homeodomain binding motifs modulate the probability of odorant receptor gene choice in transgenic mice. Mol Cell Neurosci 46: 381–396. doi: 10.1016/j.mcn.2010.11.001 21111823

19. Plessy C, Pascarella G, Bertin N, Akalin A, Carrieri C, et al. (2012) Promoter architecture of mouse olfactory receptor genes. Genome Res 22: 486–497. doi: 10.1101/gr.126201.111 22194471

20. Miller CJ, Carlson JR (2010) Regulation of Odor Receptor Genes in Trichoid Sensilla of the Drosophila Antenna. Genetics.

21. Chess A, Simon I, Cedar H, Axel R (1994) Allelic inactivation regulates olfactory receptor gene expression. Cell 78: 823–834. 8087849

22. Malnic B, Hirono J, Sato T, Buck LB (1999) Combinatorial receptor codes for odors. Cell 96: 713–723. 10089886

23. Serizawa S, Miyamichi K, Nakatani H, Suzuki M, Saito M, et al. (2003) Negative feedback regulation ensures the one receptor-one olfactory neuron rule in mouse. Science 302: 2088–2094. 14593185

24. Feinstein P, Bozza T, Rodriguez I, Vassalli A, Mombaerts P (2004) Axon guidance of mouse olfactory sensory neurons by odorant receptors and the beta2 adrenergic receptor. Cell 117: 833–846. 15186782

25. Lewcock JW, Reed RR (2004) A feedback mechanism regulates monoallelic odorant receptor expression. Proc Natl Acad Sci U S A 101: 1069–1074. 14732684

26. Dalton RP, Lyons DB, Lomvardas S (2013) Co-opting the unfolded protein response to elicit olfactory receptor feedback. Cell 155: 321–332. doi: 10.1016/j.cell.2013.09.033 24120133

27. Lyons DB, Allen WE, Goh T, Tsai L, Barnea G, et al. (2013) An epigenetic trap stabilizes singular olfactory receptor expression. Cell 154: 325–336. doi: 10.1016/j.cell.2013.06.039 23870122

28. Stewart AJ, Hannenhalli S, Plotkin JB (2012) Why transcription factor binding sites are ten nucleotides long. Genetics 192: 973–985. doi: 10.1534/genetics.112.143370 22887818

29. Jolma A, Yan J, Whitington T, Toivonen J, Nitta KR, et al. (2013) DNA-binding specificities of human transcription factors. Cell 152: 327–339. doi: 10.1016/j.cell.2012.12.009 23332764

30. Berger MF, Badis G, Gehrke AR, Talukder S, Philippakis AA, et al. (2008) Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences. Cell 133: 1266–1276. doi: 10.1016/j.cell.2008.05.024 18585359

31. Bai L, Goldman AL, Carlson JR (2009) Positive and negative regulation of odor receptor gene choice in Drosophila by acj6. J Neurosci 29: 12940–12947. doi: 10.1523/JNEUROSCI.3525-09.2009 19828808

32. Gruber CA, Rhee JM, Gleiberman A, Turner EE (1997) POU domain factors of the Brn-3 class recognize functional DNA elements which are distinctive, symmetrical, and highly conserved in evolution. Mol Cell Biol 17: 2391–2400. 9111308

33. Klemm JD, Pabo CO (1996) Oct-1 POU domain-DNA interactions: cooperative binding of isolated subdomains and effects of covalent linkage. Genes Dev 10: 27–36. 8557192

34. Andersen B, Rosenfeld MG (2001) POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease. Endocr Rev 22: 2–35. 11159814

35. Alkhori L, Ost A, Alenius M (2014) The corepressor Atrophin specifies odorant receptor expression in Drosophila. FASEB J 28: 1355–1364. doi: 10.1096/fj.13-240325 24334704

36. Hoffmann AA, Sorensen JG, Loeschcke V (2003) Adaptation of Drosophila to temperature extremes: bringing together quantitative and molecular approaches. Journal of Thermal Biology 28: 175–216.

37. Magklara A, Yen A, Colquitt BM, Clowney EJ, Allen W, et al. (2011) An epigenetic signature for monoallelic olfactory receptor expression. Cell 145: 555–570. doi: 10.1016/j.cell.2011.03.040 21529909

38. Schotta G, Ebert A, Krauss V, Fischer A, Hoffmann J, et al. (2002) Central role of Drosophila SU(VAR)3–9 in histone H3-K9 methylation and heterochromatic gene silencing. EMBO J 21: 1121–1131. 11867540

39. Buck MJ, Lieb JD (2006) A chromatin-mediated mechanism for specification of conditional transcription factor targets. Nat Genet 38: 1446–1451. 17099712

40. Kalinka AT, Varga KM, Gerrard DT, Preibisch S, Corcoran DL, et al. (2010) Gene expression divergence recapitulates the developmental hourglass model. Nature 468: 811–814. doi: 10.1038/nature09634 21150996

41. Artieri CG, Singh RS (2010) Molecular evidence for increased regulatory conservation during metamorphosis, and against deleterious cascading effects of hybrid breakdown in Drosophila. BMC Biol 8: 26. doi: 10.1186/1741-7007-8-26 20356354

42. Schmidt D, Wilson MD, Ballester B, Schwalie PC, Brown GD, et al. (2010) Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding. Science 328: 1036–1040. doi: 10.1126/science.1186176 20378774

43. Stefflova K, Thybert D, Wilson MD, Streeter I, Aleksic J, et al. (2013) Cooperativity and rapid evolution of cobound transcription factors in closely related mammals. Cell 154: 530–540. doi: 10.1016/j.cell.2013.07.007 23911320

44. Bradley RK, Li XY, Trapnell C, Davidson S, Pachter L, et al. (2010) Binding site turnover produces pervasive quantitative changes in transcription factor binding between closely related Drosophila species. PLoS Biol 8: e1000343. doi: 10.1371/journal.pbio.1000343 20351773

45. He Q, Bardet AF, Patton B, Purvis J, Johnston J, et al. (2011) High conservation of transcription factor binding and evidence for combinatorial regulation across six Drosophila species. Nat Genet 43: 414–420. doi: 10.1038/ng.808 21478888

46. Piasecki BP, Burghoorn J, Swoboda P (2010) Regulatory Factor X (RFX)-mediated transcriptional rewiring of ciliary genes in animals. Proc Natl Acad Sci U S A 107: 12969–12974. doi: 10.1073/pnas.0914241107 20615967

47. Szymanski P, Levine M (1995) Multiple modes of dorsal-bHLH transcriptional synergy in the Drosophila embryo. EMBO J 14: 2229–2238. 7774581

48. Burz DS, Rivera-Pomar R, Jackle H, Hanes SD (1998) Cooperative DNA-binding by Bicoid provides a mechanism for threshold-dependent gene activation in the Drosophila embryo. EMBO J 17: 5998–6009. 9774343

49. Erceg J, Saunders TE, Girardot C, Devos DP, Hufnagel L, et al. (2014) Subtle changes in motif positioning cause tissue-specific effects on robustness of an enhancer's activity. PLoS Genet 10: e1004060. doi: 10.1371/journal.pgen.1004060 24391522

50. Rossi FM, Kringstein AM, Spicher A, Guicherit OM, Blau HM (2000) Transcriptional control: rheostat converted to on/off switch. Mol Cell 6: 723–728. 11030351

51. Hong JW, Hendrix DA, Levine MS (2008) Shadow enhancers as a source of evolutionary novelty. Science 321: 1314. doi: 10.1126/science.1160631 18772429

52. Crocker J, Abe N, Rinaldi L, McGregor AP, Frankel N, et al. (2014) Low Affinity Binding Site Clusters Confer Hox Specificity and Regulatory Robustness. Cell.