CTCF blocks antisense transcription initiation at divergent promoters

Jing Luan, Marit W. Vermunt, Camille M. Syrett, Allison Coté, Jacob M. Tome, Haoyue Zhang, Anran Huang, Jennifer M. Luppino, Cheryl A. Keller, Belinda M. Giardine, Shiping Zhang, Margaret C. Dunagin, Zhe Zhang, Eric F. Joyce, John T. Lis, Arjun Raj, Ross C. Hardison, Gerd A. Blobel

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Transcription at most promoters is divergent, initiating at closely spaced oppositely oriented core promoters to produce sense transcripts along with often unstable upstream antisense transcripts (uasTrx). How antisense transcription is regulated and to what extent it is coordinated with sense transcription is not well understood. Here, by combining acute degradation of the multi-functional transcription factor CTCF and nascent transcription measurements, we find that CTCF specifically suppresses antisense but not sense transcription at hundreds of divergent promoters. Primary transcript RNA-FISH shows that CTCF lowers burst fraction but not burst intensity of uasTrx and that co-bursting of sense and antisense transcripts is disfavored. Genome editing, chromatin conformation studies and high-resolution transcript mapping revealed that precisely positioned CTCF directly suppresses the initiation of uasTrx, in a manner independent of its architectural function. In sum, CTCF shapes the transcriptional landscape in part by suppressing upstream antisense transcription.

Original languageEnglish (US)
Pages (from-to)1136-1144
Number of pages9
JournalNature Structural and Molecular Biology
Volume29
Issue number11
DOIs
StatePublished - Nov 2022

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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