Abstract: Allostery is well documented for proteins but less recognized for DNA-protein interactions. Here we report that specific binding of a protein on DNA is significantly stabilized or destabilized by another protein bound nearby. The ternary complex’s free energy oscillates as a function of the separation between the two proteins with a periodicity of ~10 base pairs, the helical pitch of B-form DNA, and a decay length of ~15 base pairs. The binding affinity of a protein near a DNA hairpin is similarly dependent on their separation, suggesting that deformation of the double helical structure is the origin of the DNA allostery. The physiological relevance of this phenomenon is illustrated by its effect on gene expression in live bacteria and on a transcription factor’s affinity near nucleosomes.
主要研究方向: 单分子技术已成为研究生命科学的重要手段,其终极目标之一就是在体内实时观测单分子包括生物大分子的运动,并以此在分子水平上理解生理条件下的细胞过程。我们单分子及活细胞超高分辨率成像实验室的主要方向就是开创、发展和应用新的和现有的单分子技术,包括发展超高分辨率单分子荧光成像技术和单分子操作及力学测量技术,以在单分子水平上研究活细胞,如癌细胞和干细胞的基因表达和调控,进而推动癌症治疗和干细胞研究应用。运用超分辨成像和活细胞成像,我们将与其他BIOPIC的PI合作推进以下几个方向的研究:(1)哺乳动物细胞的基因表达调控;(2)基因随机表达过程在干细胞分化中的作用;(3)运用流式细胞术、微流体技术以及高通量测序等技术把在对单细胞层次基因表达的认识提高到细胞群体、组织、和器官的层次,以理解在这些层次细胞的基因表达在细胞间是如何相互引导和协调的。
Date&Time: November 2, 2012 (Friday), 10:00–11:00 a.m.
Location: 606 Conference Room