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Guided nuclear exploration increases CTCF target search efficiency.

Anders S HansenAssaf AmitaiClaudia CattoglioRobert Tse Nan TjianXavier Darzacq
Published in: Nature chemical biology (2019)
The enormous size of mammalian genomes means that for a DNA-binding protein the number of nonspecific, off-target sites vastly exceeds the number of specific, cognate sites. How mammalian DNA-binding proteins overcome this challenge to efficiently locate their target sites is not known. Here, through live-cell single-molecule tracking, we show that CCCTC-binding factor, CTCF, is repeatedly trapped in small zones that likely correspond to CTCF clusters, in a manner that is largely dependent on an internal RNA-binding region (RBRi). We develop a new theoretical model called anisotropic diffusion through transient trapping in zones to explain CTCF dynamics. Functionally, transient RBRi-mediated trapping increases the efficiency of CTCF target search by ~2.5-fold. Overall, our results suggest a 'guided' mechanism where CTCF clusters concentrate diffusing CTCF proteins near cognate binding sites, thus increasing the local ON-rate. We suggest that local guiding may allow DNA-binding proteins to more efficiently locate their target sites.
Keyphrases
  • single molecule
  • binding protein
  • living cells
  • atomic force microscopy
  • nucleic acid
  • blood brain barrier
  • dna binding