Rxivist logo

Guided nuclear exploration increases CTCF target search efficiency

By Anders S. Hansen, Assaf Amitai, Claudia Cattoglio, Robert Tjian, Xavier Darzacq

Posted 13 Dec 2018
bioRxiv DOI: 10.1101/495457 (published DOI: 10.1038/s41589-019-0422-3)

Mammalian genomes are enormous. For a DNA-binding protein, this means that the number of non-specific, 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 in the nucleus in a manner that is largely dependent on its RNA-binding region (RBR). Integrating theory, we devise a new model, Anisotropic Diffusion through transient Trapping in Zones (ADTZ), to explain this. Functionally, transient RBR-mediated trapping increases the efficiency of CTCF target search by 2.5 fold. Since the RBR-domain also mediates CTCF clustering, 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 represent a general target search mechanism in mammalian cells.

Download data

  • Downloaded 1,264 times
  • Download rankings, all-time:
    • Site-wide: 8,136 out of 92,758
    • In biophysics: 245 out of 4,028
  • Year to date:
    • Site-wide: 31,961 out of 92,758
  • Since beginning of last month:
    • Site-wide: 41,398 out of 92,758

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News