title: Variability and memory of protein levels in human cells.
abstract: Protein expression is a stochastic process that leads to phenotypic variation among cells. The cell-cell distribution of protein levels in microorganisms has been well characterized but little is known about such variability in human cells. Here, we studied the variability of protein levels in human cells, as well as the temporal dynamics of this variability, and addressed whether cells with higher than average protein levels eventually have lower than average levels, and if so, over what timescale does this mixing occur. We measured fluctuations over time in the levels of 20 endogenous proteins in living human cells, tagged by the gene for yellow fluorescent protein at their chromosomal loci. We found variability with a standard deviation that ranged, for different proteins, from about 15% to 30% of the mean. Mixing between high and low levels occurred for all proteins, but the mixing time was longer than two cell generations (more than 40 h) for many proteins. We also tagged pairs of proteins with two colours, and found that the levels of proteins in the same biological pathway were far more correlated than those of proteins in different pathways. The persistent memory for protein levels that we found might underlie individuality in cell behaviour and could set a timescale needed for signals to affect fully every member of a cell population.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100 Israel.
authors.forename: Alex
authors.initials: A
authors.lastname: Sigal
authors.forename: Ron
authors.initials: R
authors.lastname: Milo
authors.forename: Ariel
authors.initials: A
authors.lastname: Cohen
authors.forename: Naama
authors.initials: N
authors.lastname: Geva-Zatorsky
authors.forename: Yael
authors.initials: Y
authors.lastname: Klein
authors.forename: Yuvalal
authors.initials: Y
authors.lastname: Liron
authors.forename: Nitzan
authors.initials: N
authors.lastname: Rosenfeld
authors.forename: Tamar
authors.initials: T
authors.lastname: Danon
authors.forename: Natalie
authors.initials: N
authors.lastname: Perzov
authors.forename: Uri
authors.initials: U
authors.lastname: Alon
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D025743:HMGA2 Protein / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D008856:Microscopy, Fluorescence; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7
chemical_list: D001426:Bacterial Proteins; D025743:HMGA2 Protein; D008164:Luminescent Proteins; D011506:Proteins; C054562:yellow fluorescent protein, Bacteria; D010450:Endopeptidases; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7; D004264:DNA Topoisomerases, Type I