Chromatin architecture and virulence-related gene expression in eukaryotic microbial pathogens
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A fundamental question in biology is to understand how appropriate transcriptional regulation and dense packaging of the genetic material within the eukaryotic nucleus are achieved. The exquisite gene expression control and other metabolic processes of DNA require a highly complex, multilayered, three-dimensional architecture of the chromatin and its specific compartmentalization within the nucleus. Some of these architectural and sub-nuclear positioning mechanisms have been extensively co-opted by eukaryotic pathogens to keep fine expression control and expansion of virulence-related gene families in Plasmodium falciparum, Trypanosoma brucei and Candida glabrata. For example non-linear interactions between distant cis-acting regions and the formation of chromatin loops are required for appropriate regulation of the expression of virulence-related multi-gene families encoding cell surface proteins. These gene families are located near the chromosome ends and tethered to the nuclear periphery. Consequently, only one or very few genes of the family are expressed at a time. These genes are involved in antigenic variation in parasites and the generation of subpopulations of cells with diverse antigenic proteins at the surface in some pathogenic fungi, making them highly efficient pathogens.
KeywordsDNA loop TADs Epigenetics Chromatin interactome Fungal pathogens
The authors wish to thank Alejandro De Las Peñas for critical review of the manuscript. We are indebted to Eunice López-Fuentes and Guadalupe Gutiérrez-Escobedo for helpful comments and reviewing of the manuscript. This work was supported by Consejo Nacional de Ciencia y Tecnología (CONACyT) Grant no. CB-2014-239629 to I.C.N.
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The authors declare that they have no conflict of interest.
The manuscript has been prepared following all the ethical standards of the journal.
- De Las Penas A, Pan SJ, Castano I, Alder J, Cregg R, Cormack BP (2003) Virulence-related surface glycoproteins in the yeast pathogen Candida glabrata are encoded in subtelomeric clusters and subject to RAP1- and SIR-dependent transcriptional silencing. Genes Dev 17:2245–2258. https://doi.org/10.1101/gad.1121003 CrossRefGoogle Scholar
- Erlendson AA, Friedman S, Freitag M (2017) A matter of scale and dimensions: chromatin of chromosome landmarks in the fungi. Microbiol Spectr. https://doi.org/10.1128/microbiolspec.FUNK-0054-2017 Google Scholar
- Karmodiya K, Krebs AR, Oulad-Abdelghani M, Kimura H, Tora L (2012) H3K9 and H3K14 acetylation co-occur at many gene regulatory elements, while H3K14ac marks a subset of inactive inducible promoters in mouse embryonic stem cells. BMC Genom 13:424. https://doi.org/10.1186/1471-2164-13-424 CrossRefGoogle Scholar
- Lopez-Fuentes E, Hernandez-Hernandez G, Castanedo L, Gutierrez-Escobedo G, Oktaba K, De Las Penas A, Castano I (2018b) Chromatin loop formation induced by a subtelomeric protosilencer represses EPA genes in Candida glabrata. Genetics 210:113–128. https://doi.org/10.1534/genetics.118.301202 CrossRefGoogle Scholar
- Ng HH, Ciccone DN, Morshead KB, Oettinger MA, Struhl K (2003) Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: a potential mechanism for position-effect variegation. Proc Natl Acad Sci USA 100:1820–1825. https://doi.org/10.1073/pnas.0437846100 CrossRefGoogle Scholar