title: Macromolecular Crowding Regulates the Gene Expression Profile by Limiting Diffusion.
abstract: We seek to elucidate the role of macromolecular crowding in transcription and translation. It is well known that stochasticity in gene expression can lead to differential gene expression and heterogeneity in a cell population. Recent experimental observations by Tan et al. have improved our understanding of the functional role of macromolecular crowding. It can be inferred from their observations that macromolecular crowding can lead to robustness in gene expression, resulting in a more homogeneous cell population. We introduce a spatial stochastic model to provide insight into this process. Our results show that macromolecular crowding reduces noise (as measured by the kurtosis of the mRNA distribution) in a cell population by limiting the diffusion of transcription factors (i.e. removing the unstable intermediate states), and that crowding by large molecules reduces noise more efficiently than crowding by small molecules. Finally, our simulation results provide evidence that the local variation in chromatin density as well as the total volume exclusion of the chromatin in the nucleus can induce a homogenous cell population.
authors.affiliation: Department of Mechanical Engineering, University of California, Santa Barbara, California, United States of America.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Golkaram
authors.affiliation: Department of Computer Science, University of California, Santa Barbara, California, United States of America.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hellander
authors.affiliation: Department of Computer Science, University of California, Santa Barbara, California, United States of America.
authors.forename: Brian
authors.initials: B
authors.lastname: Drawert
authors.affiliation: Department of Mechanical Engineering, University of California, Santa Barbara, California, United States of America.|Department of Computer Science, University of California, Santa Barbara, California, United States of America.
authors.forename: Linda R
authors.initials: LR
authors.lastname: Petzold
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004058:Diffusion; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry; D035683:MicroRNAs / Q000737:chemistry* / Q000235:genetics*; D008956:Models, Chemical; D008957:Models, Genetic; D015233:Models, Statistical; D014176:Protein Biosynthesis / Q000235:genetics; D013269:Stochastic Processes; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D059467:Transcriptome / Q000502:physiology
chemical_list: D046911:Macromolecular Substances; D035683:MicroRNAs; D014157:Transcription Factors