Chromosome-wide co-fluctuation of stochastic gene expression in mammalian cells

Autoři: Mengyi Sun aff001;  Jianzhi Zhang aff001
Působiště autorů: Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI, United States of America aff001
Vyšlo v časopise: Chromosome-wide co-fluctuation of stochastic gene expression in mammalian cells. PLoS Genet 15(9): e32767. doi:10.1371/journal.pgen.1008389
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008389


Gene expression is subject to stochastic noise, but to what extent and by which means such stochastic variations are coordinated among different genes are unclear. We hypothesize that neighboring genes on the same chromosome co-fluctuate in expression because of their common chromatin dynamics, and verify it at the genomic scale using allele-specific single-cell RNA-sequencing data of mouse cells. Unexpectedly, the co-fluctuation extends to genes that are over 60 million bases apart. We provide evidence that this long-range effect arises in part from chromatin co-accessibilities of linked loci attributable to three-dimensional proximity, which is much closer intra-chromosomally than inter-chromosomally. We further show that genes encoding components of the same protein complex tend to be chromosomally linked, likely resulting from natural selection for intracellular among-component dosage balance. These findings have implications for both the evolution of genome organization and optimal design of synthetic genomes in the face of gene expression noise.

Klíčová slova:

Biology and life sciences – Biochemistry – Proteins – Protein complexes – DNA-binding proteins – Histones – Genetics – Gene expression – Heredity – Genetic mapping – Linkage analysis – Epigenetics – Genomics – Animal genomics – Mammalian genomics – Genetic loci – Cell biology – Chromosome biology – Chromatin – Chromosomes – Autosomes – Chromosome pairs


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