In previous chapters, we discussed the evidence indicating that the primary control of gene expression lies at the level of transcription, with regulatory processes determining which genes are transcribed to produce the primary RNA transcript. Compared to prokaryotes, the chromosomes of eukaryotes are larger and undergo greater compaction. To understand gene control processes in compact chromosomes, it is therefore necessary to investigate the mechanisms responsible for transcriptional control in a chromosomal context.
Multiple-choice questions
Questions for Discussion
- Prokaryotic and eukaryotic chromosomes are compacted to be accommodated within cells. Compare and contrast chromosomal compaction mechanisms in prokaryotes and eukaryotes and their role in gene control.
- Discuss the role of chromosome condensation in biological evolution.
- Discuss the role of heterochromatin in protecting the human genome from viruses/
- Histone deacetylase inhibitors such as Vorinostat which relax the chromatin to also upregulate the expression of genes are approved as a cancer chemotherapy. Discuss the advantages and disadvantages of cancer therapies that relaxes chromatin.
- Discuss the evolution of insulators in the eukaryotic genomes.
Further Reading
4.1 Commitment to the differentiated state and its stability
Boltsis, I., Grosveld, F., Giraud, G., & Kolovos, P. (2021). Chromatin Conformation in Development and Disease. Frontiers in Cell and Developmental Biology, 9, 723859.
Coon H.G. (1966) Clonal stability and phenotypic expression of chick cartilage cells in vitro. Proc Natl Acad Sci USA 55:66–73.
Hadorn E (1968) Transdetermination in cells. Sci Am 219:110–120.
4.2 The nucleosome
Bracken, A. P., Brien, G. L., & Verrijzer, C. P. (2019). Dangerous liaisons: Interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancer. Genes & Development, 33(15–16), 936–959. https://doi.org/10.1101/gad.326066.119
Brahma, S., & Henikoff, S. (2020). Epigenome Regulation by Dynamic Nucleosome Unwrapping. Trends in Biochemical Sciences, 45(1), 13–26. https://doi.org/10.1016/j.tibs.2019.09.003
Brogaard, K, Xi L, Wan J.P. & Widom J (2012) A map of nucleosome positions in yeast at base-pair resolution. Nature 486:496–501.
Cairns B.R. (2009) The logic of chromatin architecture and remodelling at promoters. Nature 461:193–198.
Chen, P., Li, W., & Li, G. (2021). Structures and Functions of Chromatin Fibers. Annual Review of Biophysics, 50, 95–116. https://doi.org/10.1146/annurev-biophys-062920-063639
Khorasanizadeh S (2004) The nucleosome: from genomic organization to genomic regulation. Cell 116:259–272.
Margueron R & Reinberg D (2010) Chromatin structure and the inheritance of epigenetic information. Nat Rev Genet 11:285–296
Tan, Z. Y., Cai, S., Noble, A. J., Chen, J. K., Shi, J., & Gan, L. (2023). Heterogeneous non-canonical nucleosomes predominate in yeast cells in situ. ELife, 12, RP87672. https://doi.org/10.7554/eLife.87672
Zhang Z & Pugh B.F. (2011) High-resolution genome-wide mapping of the primary structure of chromatin. Cell 144:175–186.
4.3 Histone modifications and histone variants
Dimitrova, E., Turberfield, A. H., & Klose, R. J. (2015). Histone demethylases in chromatin biology and beyond. EMBO Reports, 16(12), 1620–1639. https://doi.org/10.15252/embr.201541113
Hyun, K., Jeon, J., Park, K., & Kim, J. (2017). Writing, erasing and reading histone lysine methylations. Experimental & Molecular Medicine, 49(4), e324. https://doi.org/10.1038/emm.2017.11
Jambhekar, A., Dhall, A., & Shi, Y. (2019). Roles and regulation of histone methylation in animal development. Nature Reviews. Molecular Cell Biology, 20(10), 625–641. https://doi.org/10.1038/s41580-019-0151-1
Kim G.W. & Yan X.J. (2011) Comprehensive lysine acetylomes emerging from bacteria to humans. Trends Biochem Sci 36:211–220.
Kurumizaka, H., Kujirai, T., & Takizawa, Y. (2021). Contributions of Histone Variants in Nucleosome Structure and Function. Journal of Molecular Biology, 433(6), 166678. https://doi.org/10.1016/j.jmb.2020.10.012
Millán-Zambrano, G., Burton, A., Bannister, A. J., & Schneider, R. (2022). Histone post-translational modifications—Cause and consequence of genome function. Nature Reviews. Genetics, 23(9), 563–580. https://doi.org/10.1038/s41576-022-00468-7
Patra, S. K. (2021). Emerging histone glutamine modifications mediated gene expression in cell differentiation and the VTA reward pathway. Gene, 768, 145323. https://doi.org/10.1016/j.gene.2020.145323
Talbert, P. B., & Henikoff, S. (2021). The Yin and Yang of Histone Marks in Transcription. Annual Review of Genomics and Human Genetics, 22, 147–170. https://doi.org/10.1146/annurev-genom-120220-085159
4.4 The 30 nm chromatin fiber
Koch, L. (2021). Chromatin control by H1 histones. Nature Reviews. Genetics, 22(2), 68–69. https://doi.org/10.1038/s41576-020-00323-72.5
Zhu, P., & Li, G. (2016). Structural insights of nucleosome and the 30-nm chromatin fiber. Current Opinion in Structural Biology, 36, 106–115. https://doi.org/10.1016/j.sbi.2016.01.013
4.5 Structural and functional domains in chromatin
Chen, D., & Lei, E. P. (2019). Function and regulation of chromatin insulators in dynamic genome organization. Current Opinion in Cell Biology, 58, 61–68. https://doi.org/10.1016/j.ceb.2019.02.001
Dehingia, B., Milewska, M., Janowski, M., & Pękowska, A. (2022). CTCF shapes chromatin structure and gene expression in health and disease. EMBO Reports, 23(9), e55146. https://doi.org/10.15252/embr.202255146
Dekker J, Marti-Renom M.A. & Mirny L.A. (2013) Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data. Nat Rev Genet 14:390–403.
Kleckner N, Zickler D & Witz G (2013) Chromosome capture brings it all together. Science 342:940–941.
de Wit E & de Laat W (2012) A decade of 3C technologies: insights into nuclear organization. Genes Dev 26:11–24.
Paul, M. R., Hochwagen, A., & Ercan, S. (2019). Condensin action and compaction. Current Genetics, 65(2), 407–415. https://doi.org/10.1007/s00294-018-0899-4
van Ruiten, M. S., & Rowland, B. D. (2021). On the choreography of genome folding: A grand pas de deux of cohesin and CTCF. Current Opinion in Cell Biology, 70, 84–90. https://doi.org/10.1016/j.ceb.2020.12.00
Sundararajan, K., & Straight, A. F. (2022). Centromere Identity and the Regulation of Chromosome Segregation. Frontiers in Cell and Developmental Biology, 10, 914249. https://doi.org/10.3389/fcell.2022.914249.
Tan L (2019) Three –dimensional genome structure of a single cell. Science 366, 964-965