As discussed in Chapter 11, the regulation of gene expression plays a key role in the early development of organisms as diverse as flies and mammals. In many cases, such regulation involves transcription factors whose synthesis is regulated so that they are only produced at a particular time during development or in a particular region of the embryo. For example, the Oct4 factor is synthesized specifically in pluripotent cells of the early embryo and is important in maintaining their pluripotent nature (see Chapter 11, Section 11.1). Similarly, in both Drosophila and mammals, homeodomain-containing transcription factors are synthesized in particular regions of the embryo and control the production of different embryonic structures (see Chapter 11, Sections 11.2 and 11.3).
Multiple-choice questions
Questions for Discussion
- Myogenin plays a crucial role in governing the differentiation of muscle cells in the early stage of embryonic development. Its expression timing should be regulated precisely to avoid early activation of muscle differentiation genes. But in embryonic cells, the myogenin gene is switched on before it’s required. Discuss different mechanisms that control the starting of early muscle differentiation programs by myogenin.
- When mouse fibroblast cells are exposed to 5-azacytidine, they differentiate into muscle cells. This differentiation is attributed to the activity of a transcription regulator called MyoD. MyoD governs the transcription of multiple genes, which turn on either early or late in the differentiation process. Interestingly, MyoD binds to the promoters of the late genes as soon as it’s expressed, but their expression is delayed. Explain different mechanisms that underlie this selective regulation of early vs. late genes by MyoD.
- In this chapter, we learned that alternative splicing plays a critical role in the functioning and plasticity of non-dividing cells, such as neurons. In this context, discuss the origin of introns and their significance in genome evolution.
- Discuss the role of non-coding RNA in establishing ordered assembly of transcription regulatory factors for tissue specific gene expression.
- Discuss the mechanism by which environmental conditions regulate the combinatorial control of transcription to determine the mating type switch in yeast.
Further Reading
12.1 Regulation of gene expression in skeletal muscle cells
Esteves de Lima, J., & Relaix, F. (2021). Master regulators of skeletal muscle lineage development and pluripotent stem cells differentiation. Cell Regeneration (London, England), 10(1), 31. https://doi.org/10.1186/s13619-021-00093-5
Maire, P., Dos Santos, M., Madani, R., Sakakibara, I., Viaut, C., & Wurmser, M. (2020). Myogenesis control by SIX transcriptional complexes. Seminars in Cell & Developmental Biology, 104, 51–64. https://doi.org/10.1016/j.semcdb.2020.03.003
Martone, J., Mariani, D., Desideri, F., & Ballarino, M. (2020). Non-coding RNAs Shaping Muscle. Frontiers in Cell and Developmental Biology, 7, 394. https://doi.org/10.3389/fcell.2019.00394
Padilla-Benavides, T., Reyes-Gutierrez, P., & Imbalzano, A. N. (2020). Regulation of the Mammalian SWI/SNF Family of Chromatin Remodeling Enzymes by Phosphorylation during Myogenesis. Biology, 9(7), 152. https://doi.org/10.3390/biology9070152
Rauch, A., & Mandrup, S. (2021). Transcriptional networks controlling stromal cell differentiation. Nature Reviews Molecular Cell Biology, 22(7), 465–482. https://doi.org/10.1038/s41580-021-00357-7
Wardle, F. C. (2019). Master control: Transcriptional regulation of mammalian Myod. Journal of Muscle Research and Cell Motility, 40(2), 211–226. https://doi.org/10.1007/s10974-019-09538-6
12.2 Regulation of gene expression in neuronal cells
Jauhari, A., & Yadav, S. (2019). MiR-34 and MiR-200: Regulator of Cell Fate Plasticity and Neural Development. Neuromolecular Medicine, 21(2), 97–109. https://doi.org/10.1007/s12017-019-08535-9
Lipscombe, D., & Lopez Soto, E. J. (2019). Alternative splicing of neuronal genes: New mechanisms and new therapies. Current Opinion in Neurobiology, 57, 26–31. https://doi.org/10.1016/j.conb.2018.12.013
Maire, P., Dos Santos, M., Madani, R., Sakakibara, I., Viaut, C., & Wurmser, M. (2020). Myogenesis control by SIX transcriptional complexes. Seminars in Cell & Developmental Biology, 104, 51–64. https://doi.org/10.1016/j.semcdb.2020.03.003
Maksour, S., Ooi, L., & Dottori, M. (2020). More than a Corepressor: The Role of CoREST Proteins in Neurodevelopment. eNeuro, 7(2), ENEURO.0337-19.2020. https://doi.org/10.1523/ENEURO.0337-19.2020
Martone, J., Mariani, D., Desideri, F., & Ballarino, M. (2020). Non-coding RNAs Shaping Muscle. Frontiers in Cell and Developmental Biology, 7, 394. https://doi.org/10.3389/fcell.2019.00394
Matsubara, S., Matsuda, T., & Nakashima, K. (2021). Regulation of Adult Mammalian Neural Stem Cells and Neurogenesis by Cell Extrinsic and Intrinsic Factors. Cells, 10(5), 1145. https://doi.org/10.3390/cells10051145
Nord, A. S., & West, A. E. (2020). Neurobiological functions of transcriptional enhancers. Nature Neuroscience, 23(1), 5–14. https://doi.org/10.1038/s41593-019-0538-5
Padilla-Benavides, T., Reyes-Gutierrez, P., & Imbalzano, A. N. (2020). Regulation of the Mammalian SWI/SNF Family of Chromatin Remodeling Enzymes by Phosphorylation during Myogenesis. Biology, 9(7), 152. https://doi.org/10.3390/biology9070152
Porter, R. S., & Iwase, S. (2023). Modulation of chromatin architecture influences the neuronal nucleus through activity-regulated gene expression. Biochemical Society Transactions, 51(2), 703–713. https://doi.org/10.1042/BST20220889
Rauch, A., & Mandrup, S. (2021). Transcriptional networks controlling stromal cell differentiation. Nature Reviews Molecular Cell Biology, 22(7), 465–482. https://doi.org/10.1038/s41580-021-00357-7
Sousa, E., & Flames, N. (2022). Transcriptional regulation of neuronal identity. The European Journal of Neuroscience, 55(3), 645–660. https://doi.org/10.1111/ejn.15551
VandenBosch, L. S., & Reh, T. A. (2020). Epigenetics in neuronal regeneration. Seminars in Cell & Developmental Biology, 97, 63–73. https://doi.org/10.1016/j.semcdb.2019.04.001
Wardle, F. C. (2019). Master control: Transcriptional regulation of mammalian Myod. Journal of Muscle Research and Cell Motility, 40(2), 211–226. https://doi.org/10.1007/s10974-019-09538-6
12.3 Regulation of yeast mating type
Booth L.N., Tuch B.B. & Johnson A.D. (2010) Intercalation of a new tier of transcription regulation into an ancient circuit. Nature 468:959–965.
Herskowitz I (1989) A regulatory hierarchy for cell specialization in yeast. Nature 342:749–757.
Rimal, A., & Winter, E. (2022). Meiotic commitment: More than a transcriptional switch. Current Biology: CB, 32(7), R320–R322. https://doi.org/10.1016/j.cub.2022.02.064
Thon, G., Maki, T., Haber, J. E., & Iwasaki, H. (2019). Mating-type switching by homology-directed recombinational repair: A matter of choice. Current Genetics, 65(2), 351–362. https://doi.org/10.1007/s00294-018-0900-2
Yu, Y., Yarrington, R. M., & Stillman, D. J. (2020). FACT and Ash1 promote long-range and bidirectional nucleosome eviction at the HO promoter. Nucleic Acids Research, 48(19), 10877–10889. https://doi.org/10.1093/nar/gkaa819