Silencing Is Noisy: Population and Cell Level Noise in Telomere-Adjacent Genes Is Dependent on Telomere Position and Sir2
Genetic diversity is often high at telomeres, the chromosome ends where genes are readily amplified and modified. Phenotypic diversity, e.g., growth properties under a given condition, is affected by stochastic variations in gene expression exhibited among cells in a homogenous environment. Our studies found that individual subtelomeric genes show high variability of gene expression both between cells within a single population and also between separate sub-populations. Cell-to-cell variation, termed Telomere-Adjacent Gene Expression Noise (TAGEN), affected single telomeric genes. We found that classical telomeric silencing and TAGEN are tightly linked, with both being dependent upon proximity to telomeres and the Sir2 chromatin modifying enzyme. In addition, both are coordinately regulated locally—at the DNA level: at a telomere with transcription that is continually silenced or activated, the level of expression variability is reduced. This work provides experimental support for computational work that predicted this relationship between stochastic chromatin silencing and expression plasticity at each telomere individually. Furthermore, it demonstrates that these shifts affect the degree of cell-to cell noise of telomere-adjacent loci.
Vyšlo v časopise:
Silencing Is Noisy: Population and Cell Level Noise in Telomere-Adjacent Genes Is Dependent on Telomere Position and Sir2. PLoS Genet 10(7): e32767. doi:10.1371/journal.pgen.1004436
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1004436
Souhrn
Genetic diversity is often high at telomeres, the chromosome ends where genes are readily amplified and modified. Phenotypic diversity, e.g., growth properties under a given condition, is affected by stochastic variations in gene expression exhibited among cells in a homogenous environment. Our studies found that individual subtelomeric genes show high variability of gene expression both between cells within a single population and also between separate sub-populations. Cell-to-cell variation, termed Telomere-Adjacent Gene Expression Noise (TAGEN), affected single telomeric genes. We found that classical telomeric silencing and TAGEN are tightly linked, with both being dependent upon proximity to telomeres and the Sir2 chromatin modifying enzyme. In addition, both are coordinately regulated locally—at the DNA level: at a telomere with transcription that is continually silenced or activated, the level of expression variability is reduced. This work provides experimental support for computational work that predicted this relationship between stochastic chromatin silencing and expression plasticity at each telomere individually. Furthermore, it demonstrates that these shifts affect the degree of cell-to cell noise of telomere-adjacent loci.
Zdroje
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