Distinct properties and functions of CTCF revealed by a rapidly inducible degron system

Cell Rep. 2021 Feb 23;34(8):108783. doi: 10.1016/j.celrep.2021.108783.


CCCTC-binding factor (CTCF) is a conserved zinc finger transcription factor implicated in a wide range of functions, including genome organization, transcription activation, and elongation. To explore the basis for CTCF functional diversity, we coupled an auxin-induced degron system with precision nuclear run-on. Unexpectedly, oriented CTCF motifs in gene bodies are associated with transcriptional stalling in a manner independent of bound CTCF. Moreover, CTCF at different binding sites (CBSs) displays highly variable resistance to degradation. Motif sequence does not significantly predict degradation behavior, but location at chromatin boundaries and chromatin loop anchors, as well as co-occupancy with cohesin, are associated with delayed degradation. Single-molecule tracking experiments link chromatin residence time to CTCF degradation kinetics, which has ramifications regarding architectural CTCF functions. Our study highlights the heterogeneity of CBSs, uncovers properties specific to architecturally important CBSs, and provides insights into the basic processes of genome organization and transcription regulation.

Keywords: CTCF; PRO-seq; chromatin architecture; cohesin; degradation dynamics; residence time; single-molecule tracking; transcription elongation stalling.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding Sites
  • CCCTC-Binding Factor / genetics
  • CCCTC-Binding Factor / metabolism*
  • CRISPR-Cas Systems
  • Cell Line
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly
  • Chromatin Immunoprecipitation Sequencing*
  • Erythroblasts / metabolism*
  • Gene Editing
  • Kinetics
  • Mice
  • Molecular Dynamics Simulation
  • Protein Binding
  • Proteolysis
  • RNA Polymerase II / metabolism
  • Single Molecule Imaging*
  • Transcription, Genetic


  • CCCTC-Binding Factor
  • Chromatin
  • Ctcf protein, mouse
  • RNA Polymerase II