title: RNA Polymerase II cluster dynamics predict mRNA output in living cells.
abstract: Protein clustering is a hallmark of genome regulation in mammalian cells. However, the dynamic molecular processes involved make it difficult to correlate clustering with functional consequences in vivo. We developed a live-cell super-resolution approach to uncover the correlation between mRNA synthesis and the dynamics of RNA Polymerase II (Pol II) clusters at a gene locus. For endogenous β-actin genes in mouse embryonic fibroblasts, we observe that short-lived (~8 s) Pol II clusters correlate with basal mRNA output. During serum stimulation, a stereotyped increase in Pol II cluster lifetime correlates with a proportionate increase in the number of mRNAs synthesized. Our findings suggest that transient clustering of Pol II may constitute a pre-transcriptional regulatory event that predictably modulates nascent mRNA output.
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Won-Ki
authors.identifier: 0000-0001-9336-0686
authors.initials: WK
authors.lastname: Cho
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Namrata
authors.initials: N
authors.lastname: Jayanth
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Brian P
authors.initials: BP
authors.lastname: English
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Takuma
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: J Owen
authors.initials: JO
authors.lastname: Andrews
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: William
authors.initials: W
authors.lastname: Conway
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Grimm
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Spille
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Luke D
authors.initials: LD
authors.lastname: Lavis
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Timothée
authors.initials: T
authors.lastname: Lionnet
authors.affiliation: Department of Physics, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Ibrahim I
authors.identifier: 0000-0002-8764-1809
authors.initials: II
authors.lastname: Cisse
mesh_terms: D000199:Actins / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000502:physiology; D005786:Gene Expression Regulation; D056426:Genetic Loci; D051379:Mice; D012319:RNA Polymerase II / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis*
chemical_list: D000199:Actins; D012333:RNA, Messenger; D012319:RNA Polymerase II
keywords: RNA Polymerase II; biophysics; bursting; chromosomes; clustering; gene expression; genes; mRNA; mouse; structural biology; transcription