Saiz Leonor, Rubi J Miguel, Vilar Jose M G
Integrative Biological Modeling Laboratory, Computational Biology Program, Memorial Sloan-Kettering Cancer Center, 307 East 63rd Street, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17642-5. doi: 10.1073/pnas.0505693102. Epub 2005 Nov 22.
The free energy of looping DNA by proteins and protein complexes determines to what extent distal DNA sites can affect each other. We inferred its in vivo value through a combined computational-experimental approach for different lengths of the loop and found that, in addition to the intrinsic periodicity of the DNA double helix, the free energy has an oscillatory component of about half the helical period. Moreover, the oscillations have such an amplitude that the effects of regulatory molecules become strongly dependent on their precise DNA positioning and yet easily tunable by their cooperative interactions. These unexpected results can confer to the physical properties of DNA a more prominent role at shaping the properties of gene regulation than previously thought.
蛋白质和蛋白质复合物使DNA成环的自由能决定了远端DNA位点相互影响的程度。我们通过针对不同环长度的计算与实验相结合的方法推断了其体内值,发现除了DNA双螺旋的固有周期性外,自由能还有一个约为螺旋周期一半的振荡成分。此外,这些振荡的幅度使得调节分子的作用强烈依赖于它们在DNA上的精确位置,但又很容易通过它们的协同相互作用进行调节。这些意想不到的结果表明,DNA的物理特性在塑造基因调控特性方面所起的作用比之前认为的更为显著。