@article{fd1a4258822d4838acce61e63716ccbc,
title = "CTCF blocks antisense transcription initiation at divergent promoters",
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.",
author = "Jing Luan and Vermunt, {Marit W.} and Syrett, {Camille M.} and Allison Cot{\'e} and Tome, {Jacob M.} and Haoyue Zhang and Anran Huang and Luppino, {Jennifer M.} and Keller, {Cheryl A.} and Giardine, {Belinda M.} and Shiping Zhang and Dunagin, {Margaret C.} and Zhe Zhang and Joyce, {Eric F.} and Lis, {John T.} and Arjun Raj and Hardison, {Ross C.} and Blobel, {Gerd A.}",
note = "Funding Information: We want to express our gratitude to anonymous referees for their valuable and constructive comments. This work was sponsored by Natural Science Foundation of Hebei Province under Grant Nos. A2022210002 and A2021210027, and the National Natural Science Foundation of China under Grant No. 12001480. Funding Information: We are grateful to Hardison, Raj, Lis and Blobel laboratories for insightful discussions. We thank the staff at the flow cytometry core of The Children{\textquoteright}s Hospital of Philadelphia. This work was supported by NIH grants no. R01 DK58044 to G.A.B., R24 DK106766 to G.A.B. and R.C.H., T32 HL07439 to C.M.S., R01GM121613 to R.C.H. and U01 DK127405 to G.A.B. and A.R., an EMBO long-term fellowship (ALTF 540-2018) to M.W.V. and an American Heart Association postdoctoral fellowship 836074 to M.W.V. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
month = nov,
doi = "10.1038/s41594-022-00855-y",
language = "English (US)",
volume = "29",
pages = "1136--1144",
journal = "Nature Structural Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "11",
}