Gene Control

Third Edition

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Chapter 15: Conclusions

The pioneering studies of Jacob and Monod on the Lac operon in the 1950s led to a body of work on the regulation of gene expression in bacteria. These studies established for the first time that regulatory proteins could bind to DNA and influence gene transcription either positively or negatively. This allows, for example, operons containing genes encoding proteins required to break down particular substrates to be transcriptionally activated in response to the presence of the substrate. Similarly, operons containing genes encoding proteins needed to synthesize a particular substance could be transcriptionally silenced when that substance was available to the bacteria from its environment (for the full discussion of these mechanisms see Chapters 2 and 3).

Multiple-choice questions

Questions for Discussion

  1. Compare and contrast prokaryotic and eukaryotic gene regulation and discuss the evolution of DNA and histone modifications in gene control.
  2. The increasing complexity of organisms from bacteria to unicellular eukaryotes to mammals cannot be accounted for solely by the number of protein-coding genes. What other factors contribute to the complexity of higher organisms, given the relatively small number of identified mammalian genes?
  3. Discuss the role of non-coding RNAs and alternative splicing in the formation of spatial and temporal memory formation in brain cells.
  4. Discuss the significance of enhancers and mediator complexes in the evolution of complex organisms.
  5. Discuss how transcription factors control the gene regulatory networks that dictate cell fate decisions during development.

Further Reading

Aldinger, K. A., Thomson, Z., Phelps, I. G., Haldipur, P., Deng, M., Timms, A. E., Hirano, M., Santpere, G., Roco, C., Rosenberg, A. B., Lorente-Galdos, B., Gulden, F. O., O’Day, D., Overman, L. M., Lisgo, S. N., Alexandre, P., Sestan, N., Doherty, D., Dobyns, W. B., … Millen, K. J. (2021). Spatial and cell type transcriptional landscape of human cerebellar development. Nature Neuroscience, 24(8), 1163–1175. https://doi.org/10.1038/s41593-021-00872-y

Beer, M. A., Shigaki, D., & Huangfu, D. (2020). Enhancer Predictions and Genome-Wide Regulatory Circuits. Annual Review of Genomics and Human Genetics, 21(Volume 21, 2020), 37–54. https://doi.org/10.1146/annurev-genom-121719-010946

Braun, E., Danan-Gotthold, M., Borm, L. E., Lee, K. W., Vinsland, E., Lönnerberg, P., Hu, L., Li, X., He, X., Andrusivová, Ž., Lundeberg, J., Barker, R. A., Arenas, E., Sundström, E., & Linnarsson, S. (2023). Comprehensive cell atlas of the first-trimester developing human brain. Science, 382(6667), eadf1226. https://doi.org/10.1126/science.adf1226

Flores-Concha, M., & Oñate, Á. A. (2020). Long Non-coding RNAs in the Regulation of the Immune Response and Trained Immunity. Frontiers in Genetics, 11. https://doi.org/10.3389/fgene.2020.00718

Gasperini, M., Tome, J. M., & Shendure, J. (2020). Towards a comprehensive catalogue of validated and target-linked human enhancers. Nature Reviews Genetics, 21(5), 292–310. https://doi.org/10.1038/s41576-019-0209-0

González-Velasco, O., Papy-García, D., Le Douaron, G., Sánchez-Santos, J. M., & De Las Rivas, J. (2020). Transcriptomic landscape, gene signatures and regulatory profile of aging in the human brain. Biochimica et Biophysica Acta (BBA) – Gene Regulatory Mechanisms, 1863(6), 194491. https://doi.org/10.1016/j.bbagrm.2020.194491

Hafner, A., & Boettiger, A. (2023). The spatial organization of transcriptional control. Nature Reviews Genetics, 24(1), 53–68. https://doi.org/10.1038/s41576-022-00526-0

Imada, E. L., Sanchez, D. F., Collado-Torres, L., Wilks, C., Matam, T., Dinalankara, W., Stupnikov, A., Lobo-Pereira, F., Yip, C.-W., Yasuzawa, K., Kondo, N., Itoh, M., Suzuki, H., Kasukawa, T., Hon, C.-C., Hoon, M. J. L. de, Shin, J. W., Carninci, P., Jaffe, A. E., … Marchionni, L. (2020). Recounting the FANTOM CAGE-Associated Transcriptome. Genome Research, 30(7), 1073–1081. https://doi.org/10.1101/gr.254656.119

Snyder, M. P., Gingeras, T. R., Moore, J. E., Weng, Z., Gerstein, M. B., Ren, B., Hardison, R. C., Stamatoyannopoulos, J. A., Graveley, B. R., Feingold, E. A., Pazin, M. J., Pagan, M., Gilchrist, D. A., Hitz, B. C., Cherry, J. M., Bernstein, B. E., Mendenhall, E. M., Zerbino, D. R., Frankish, A., … Myers, R. M. (2020). Perspectives on ENCODE. Nature, 583(7818), 693–698. https://doi.org/10.1038/s41586-020-2449-8

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