DNA dynamics play a role as a basal transcription factor in the positioning and regulation of gene transcription initiation.
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.
Alexandrov
Boian S
BS
Los Alamos National Laboratory, Theoretical Division and Center for Nonlinear Studies, Los Alamos, NM, USA.
Gelev
Vladimir
V
Yoo
Sang Wook
SW
Alexandrov
Ludmil B
LB
Fukuyo
Yayoi
Y
Bishop
Alan R
AR
Rasmussen
Kim Ø
KØ
Usheva
Anny
A
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
D014157:Transcription Factors; D004247:DNA