As discussed in Chapter 1 (Section 1.5), a variety of evidence demonstrates that gene regulation primarily operates at the level of transcription, determining which genes will be transcribed into RNA in specific tissues or in response to specific stimuli. In eukaryotes, such transcriptional control operates in part at the level of chromatin structure so that the DNA that is to be transcribed moves to a more open chromatin structure allowing access to regulatory molecules (see Chapters 4 and 5).
Multiple-choice questions
Questions for Discussion
- Discuss the coordination between gene regulation and regulatory networks in enabling cells and organisms to function and adapt to changing environments.
- Discuss similarities and differences between prokaryotc vs eukaryotic gene transcription/
- For protein production three types of RNA rRNA, mRNA, and tRNA are required. In prokaryotes, all three RNAs are transcribed by single RNA polymerase. On the other hand, in eularyotes these three types of RNAs are transcribed by three different RNA polymerases. Discuss, how RNA polymerase I, II, and III coordinate their activity to regulate protein production.
- Both prokaryotic and eukaryotic RNA polymerases lack specific DNA binding activity. Discuss the transcription factors which provides DNA binding specificity to RNA polymerases in prokaryotes and eukaryotes.
- Discuss how chromatin structure protect eukaryotic cells from invading viruses.
Further Reading
6.1 Transcription by RNA polymerases
Bhuiyan T and Trimmers HTM (2019) Promoter recognition: Puttign TFIID on Ae spot. Trends in Cell Biology 29 (9) 752-763
Cramer, P. (2019). Organization and regulation of gene transcription. Nature, 573(7772), 45–54. https://doi.org/10.1038/s41586-019-1517-4
Girbig, M., Misiaszek, A. D., & Müller, C. W. (2022). Structural insights into nuclear transcription by eukaryotic DNA-dependent RNA polymerases. Nature Reviews. Molecular Cell Biology, 23(9), 603–622. https://doi.org/10.1038/s41580-022-00476-9
Haag J.R. & Pikaard C.S. (2011) Multisubunit RNA polymerases IV and V: purveyors of noncoding RNA for plant gene silencing. Nat Rev Mol Cell Biol 12:483–492.
Iarovaia OU, Minna EP Sheval EV Onichtehouk D, Dokudouaskaya S, Razin SV and Vassetzky YS (2019) Nucleolus: A central hub for nuclear functions Trends in Cell Biology 29 (8) 647-659.
Meyer, S., Reverchon, S., Nasser, W., & Muskhelishvili, G. (2018). Chromosomal organization of transcription: In a nutshell. Current Genetics, 64(3), 555–565. https://doi.org/10.1007/s00294-017-0785-5
Roeder, R. G. (2019). 50+ years of eukaryotic transcription: An expanding universe of factors and mechanisms. Nature Structural & Molecular Biology, 26(9), 783–791. https://doi.org/10.1038/s41594-019-0287-x
Rymen, B., Ferrafiat, L., & Blevins, T. (n.d.). Non-coding RNA polymerases that silence transposable elements and reprogram gene expression in plants. Transcription, 11(3–4), 172–191. https://doi.org/10.1080/21541264.2020.1825906
Schier, A. C., & Taatjes, D. J. (2020). Structure and mechanism of the RNA polymerase II transcription machinery. Genes & Development, 34(7–8), 465–488. https://doi.org/10.1101/gad.335679.119
6.2 Transcriptional elongation and termination
Eaton, J. D., & West, S. (2020). Termination of Transcription by RNA Polymerase II: BOOM! Trends in Genetics: TIG, 36(9), 664–675. https://doi.org/10.1016/j.tig.2020.05.008
Fujinaga, K., Huang, F., & Peterlin, B. M. (2023). P-TEFb: The master regulator of transcription elongation. Molecular Cell, 83(3), 393–403. https://doi.org/10.1016/j.molcel.2022.12.006
Mohamed, A. A., Vazquez Nunez, R., & Vos, S. M. (2022). Structural advances in transcription elongation. Current Opinion in Structural Biology, 75, 102422. https://doi.org/10.1016/j.sbi.2022.102422
Kujirai, T., Ehara, H., Sekine, S.-I., & Kurumizaka, H. (2023). Structural Transition of the Nucleosome during Transcription Elongation. Cells, 12(10), 1388. https://doi.org/10.3390/cells12101388
Noe Gonzalez, M., Blears, D., & Svejstrup, J. Q. (2021). Causes and consequences of RNA polymerase II stalling during transcript elongation. Nature Reviews. Molecular Cell Biology, 22(1), 3–21. https://doi.org/10.1038/s41580-020-00308-8
Svetlov, V., & Nudler, E. (2020). Towards the unified principles of transcription termination. The EMBO Journal, 39(3), e104112. https://doi.org/10.15252/embj.2019104112
Xie, J., Libri, D., & Porrua, O. (2023). Mechanisms of eukaryotic transcription termination at a glance. Journal of Cell Science, 136(1), jcs259873. https://doi.org/10.1242/jcs.259873
6.3 The gene promoter
Cramer, P. (2019). Organization and regulation of gene transcription. Nature, 573(7772), 45–54. https://doi.org/10.1038/s41586-019-1517-4
Gomez-Pastor, R., Burchfiel, E. T., & Thiele, D. J. (2018). Regulation of heat shock transcription factors and their roles in physiology and disease. Nature Reviews. Molecular Cell Biology, 19(1), 4–19. https://doi.org/10.1038/nrm.2017.73
Haberle, V., & Stark, A. (2018). Eukaryotic core promoters and the functional basis of transcription initiation. Nature Reviews. Molecular Cell Biology, 19(10), 621–637. https://doi.org/10.1038/s41580-018-0028-8
Jiang, S., & Mortazavi, A. (2018). Integrating ChIP-seq with other functional genomics data. Briefings in Functional Genomics, 17(2), 104–115. https://doi.org/10.1093/bfgp/ely002
Kmiecik, S. W., & Mayer, M. P. (2022). Molecular mechanisms of heat shock factor 1 regulation. Trends in Biochemical Sciences, 47(3), 218–234. https://doi.org/10.1016/j.tibs.2021.10.004
Marand, A. P., & Schmitz, R. J. (2022). Single-cell analysis of cis-regulatory elements. Current Opinion in Plant Biology, 65, 102094. https://doi.org/10.1016/j.pbi.2021.102094
Schoenfelder, S., & Fraser, P. (2019). Long-range enhancer-promoter contacts in gene expression control. Nature Reviews. Genetics, 20(8), 437–455. https://doi.org/10.1038/s41576-019-0128-0
Tsytsarev, V. (2022). Methodological aspects of studying the mechanisms of consciousness. Behavioural Brain Research, 419, 113684. https://doi.org/10.1016/j.bbr.2021.113684 Dowell R.D. (2010) Transcription factor binding variation in the evolution of gene regulation. Trends Genet 26:468–475.
6.4 Enhancers and silencers
Anderson R al Sandelin A (2020) Detemenants of enhancer and promoter activity of regulatory elements Nature Review Genetics 21, 71-87.
Bozek, M., & Gompel, N. (2020). Developmental Transcriptional Enhancers: A Subtle Interplay between Accessibility and Activity: Considering Quantitative Accessibility Changes between Different Regulatory States of an Enhancer Deconvolutes the Complex Relationship between Accessibility and Activity. BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology, 42(4), e1900188. https://doi.org/10.1002/bies.201900188
Daman, A. W., & Josefowicz, S. Z. (2021). Epigenetic and transcriptional control of interferon-β. The Journal of Experimental Medicine, 218(9), e20210039. https://doi.org/10.1084/jem.20210039
Kim, S., & Wysocka, J. (2023). Deciphering the multi-scale, quantitative cis-regulatory code. Molecular Cell, 83(3), 373–392. https://doi.org/10.1016/j.molcel.2022.12.032
Kreibich, E., & Krebs, A. R. (2023). Relevance of DNA methylation at enhancers for the acquisition of cell identities. FEBS Letters, 597(14), 1805–1817. https://doi.org/10.1002/1873-3468.14686
Maldonado, R., & Längst, G. (2023). The chromatin—Triple helix connection. Biological Chemistry. https://doi.org/10.1515/hsz-2023-0189
Pang B ad Snyder MP (2020) Systematic identification of sillencers in human cells. Nature Genetics 52 254-263.
Segert, J. A., Gisselbrecht, S. S., & Bulyk, M. L. (2021). Transcriptional Silencers: Driving Gene Expression with the Brakes On. Trends in Genetics: TIG, 37(6), 514–527. https://doi.org/10.1016/j.tig.2021.02.002