Nucleosome positioning and kinetics near transcription-start-site barriers are controlled by interplay between active remodeling and DNA sequence.
We investigate how DNA sequence, ATP-dependent chromatin remodeling and nucleosome-depleted 'barriers' co-operate to determine the kinetics of nucleosome organization, in a stochastic model of nucleosome positioning and dynamics. We find that 'statistical' positioning of nucleosomes against 'barriers', hypothesized to control chromatin structure near transcription start sites, requires active remodeling and therefore cannot be described using equilibrium statistical mechanics. We show that, unlike steady-state occupancy, DNA site exposure kinetics near a barrier is dominated by DNA sequence rather than by proximity to the barrier itself. The timescale for formation of positioning patterns near barriers is proportional to the timescale for active nucleosome eviction. We also show that there are strong gene-to-gene variations in nucleosome positioning near barriers, which are eliminated by averaging over many genes. Our results suggest that measurement of nucleosome kinetics can reveal information about sequence-dependent regulation that is not apparent in steady-state nucleosome occupancy.
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India, Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA, Department of Physics and Astronomy, Northwestern University, Evanston, IL 60208, USA and Wadhwani Research Centre for Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.
Jyotsana J
JJ
Parmar
John F
JF
Marko
Ranjith
R
Padinhateeri
D001483:Base Sequence; D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000737:chemistry*; D007700:Kinetics; D008957:Models, Genetic; D009707:Nucleosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D024363:Transcription Initiation Site
D009707:Nucleosomes; D004247:DNA