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

Jing Luan, Guanjue Xiang, Pablo Aurelio Gómez-García, Jacob M. Tome, Zhe Zhang, Marit W. Vermunt, Haoyue Zhang, Anran Huang, Cheryl A. Keller, Belinda M. Giardine, Yu Zhang, Yemin Lan, John T. Lis, Melike Lakadamyali, Ross C. Hardison, Gerd A. Blobel

Research output: Contribution to journalArticlepeer-review

Abstract

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. Using an inducible CTCF degradation approach, Luan et al. show that sensitivity to degradation of CTCF on chromatin is highly variable, reflecting its diverse roles in chromatin architecture and transcription.

Original languageEnglish (US)
Article number108783
JournalCell Reports
Volume34
Issue number8
DOIs
StatePublished - Feb 23 2021

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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