title: DNA dynamics play a role as a basal transcription factor in the positioning and regulation of gene transcription initiation.
abstract: We assess the role of DNA breathing dynamics as a determinant of promoter strength and transcription start site (TSS) location. We compare DNA Langevin dynamic profiles of representative gene promoters, calculated with the extended non-linear PBD model of DNA with experimental data on transcription factor binding and transcriptional activity. Our results demonstrate that DNA dynamic activity at the TSS can be suppressed by mutations that do not affect basal transcription factor binding-DNA contacts. We use this effect to establish the separate contributions of transcription factor binding and DNA dynamics to transcriptional activity. Our results argue against a purely 'transcription factor-centric' view of transcription initiation, suggesting that both DNA dynamics and transcription factor binding are necessary conditions for transcription initiation.
authors.affiliation: Los Alamos National Laboratory, Theoretical Division and Center for Nonlinear Studies, Los Alamos, NM, USA.
authors.forename: Boian S
authors.initials: BS
authors.lastname: Alexandrov
authors.forename: Vladimir
authors.initials: V
authors.lastname: Gelev
authors.forename: Sang Wook
authors.initials: SW
authors.lastname: Yoo
authors.forename: Ludmil B
authors.initials: LB
authors.lastname: Alexandrov
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Fukuyo
authors.forename: Alan R
authors.initials: AR
authors.lastname: Bishop
authors.forename: Kim Ø
authors.initials: KØ
authors.lastname: Rasmussen
authors.forename: Anny
authors.initials: A
authors.lastname: Usheva
mesh_terms: D003198:Computer Simulation; D004247:DNA / Q000737:chemistry; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors; D004247:DNA