Diffusive hidden Markov model characterization of DNA looping dynamics in tethered particle experiments

被引:11
作者
Beausang, John F. [1 ]
Nelson, Philip C. [1 ]
机构
[1] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA
基金
美国国家科学基金会;
关键词
D O I
10.1088/1478-3975/4/3/007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In many biochemical processes, proteins bound to DNA at distant sites are brought into close proximity by loops in the underlying DNA. For example, the function of some gene-regulatory proteins depends on such 'DNA looping' interactions. We present a new technique for characterizing the kinetics of loop formation in vitro, as observed using the tethered particle method, and apply it to experimental data on looping induced by lambda repressor. Our method uses a modified ('diffusive') hidden Markov analysis that directly incorporates the Brownian motion of the observed tethered bead. We compare looping lifetimes found with our method ( which we find are consistent over a range of sampling frequencies) to those obtained via the traditional threshold-crossing analysis ( which can vary depending on how the raw data are filtered in the time domain). Our method does not involve any time filtering and can detect sudden changes in looping behavior. For example, we show how our method can identify transitions between long-lived, kinetically distinct states that would otherwise be difficult to discern.
引用
收藏
页码:205 / 219
页数:15
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