title: Nucleosomal elements that control the topography of the barrier to transcription.
abstract: The nucleosome represents a mechanical barrier to transcription that operates as a general regulator of gene expression. We investigate how each nucleosomal component-the histone tails, the specific histone-DNA contacts, and the DNA sequence-contributes to the strength of the barrier. Removal of the tails favors progression of RNA polymerase II into the entry region of the nucleosome by locally increasing the wrapping-unwrapping rates of the DNA around histones. In contrast, point mutations that affect histone-DNA contacts at the dyad abolish the barrier to transcription in the central region by decreasing the local wrapping rate. Moreover, we show that the nucleosome amplifies sequence-dependent transcriptional pausing, an effect mediated through the structure of the nascent RNA. Each of these nucleosomal elements controls transcription elongation by affecting distinctly the density and duration of polymerase pauses, thus providing multiple and alternative mechanisms for control of gene expression by chromatin remodeling and transcription factors.
authors.affiliation: Jason L. Choy Laboratory of Single-Molecule Biophysics and Department of Physics, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Lacramioara
authors.initials: L
authors.lastname: Bintu
authors.affiliation: QB3 Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Toyotaka
authors.initials: T
authors.lastname: Ishibashi
authors.affiliation: Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Manchuta
authors.initials: M
authors.lastname: Dangkulwanich
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Yueh-Yi
authors.initials: YY
authors.lastname: Wu
authors.affiliation: NCI Center for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Lubkowska
authors.affiliation: NCI Center for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Kashlev
authors.affiliation: Jason L. Choy Laboratory of Single-Molecule Biophysics and Department of Physics, University of California, Berkeley, Berkeley, CA 94720, USA; QB3 Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: carlos@alice.berkeley.edu.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bustamante
mesh_terms: D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D009707:Nucleosomes; D012319:RNA Polymerase II / Q000378:metabolism; D014158:Transcription, Genetic; D015003:Yeasts / Q000235:genetics* / Q000378:metabolism
chemical_list: D006657:Histones; D009707:Nucleosomes; D004247:DNA; D012319:RNA Polymerase II