NF-Y controls fidelity of transcription initiation at gene promoters through maintenance of the nucleosome-depleted region

Andrew J. Oldfield (), Telmo Henriques, Dhirendra Kumar, Adam B. Burkholder, Senthilkumar Cinghu, Damien Paulet, Brian D. Bennett, Pengyi Yang, Benjamin S. Scruggs, Christopher A. Lavender, Eric Rivals, Karen Adelman () and Raja Jothi ()
Additional contact information
Andrew J. Oldfield: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park
Telmo Henriques: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park
Dhirendra Kumar: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park
Adam B. Burkholder: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park
Senthilkumar Cinghu: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park
Damien Paulet: LIRMM, CNRS et Université de Montpellier
Brian D. Bennett: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park
Pengyi Yang: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park
Benjamin S. Scruggs: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park
Christopher A. Lavender: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park
Eric Rivals: LIRMM, CNRS et Université de Montpellier
Karen Adelman: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park
Raja Jothi: National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract Faithful transcription initiation is critical for accurate gene expression, yet the mechanisms underlying specific transcription start site (TSS) selection in mammals remain unclear. Here, we show that the histone-fold domain protein NF-Y, a ubiquitously expressed transcription factor, controls the fidelity of transcription initiation at gene promoters in mouse embryonic stem cells. We report that NF-Y maintains the region upstream of TSSs in a nucleosome-depleted state while simultaneously protecting this accessible region against aberrant and/or ectopic transcription initiation. We find that loss of NF-Y binding in mammalian cells disrupts the promoter chromatin landscape, leading to nucleosomal encroachment over the canonical TSS. Importantly, this chromatin rearrangement is accompanied by upstream relocation of the transcription pre-initiation complex and ectopic transcription initiation. Further, this phenomenon generates aberrant extended transcripts that undergo translation, disrupting gene expression profiles. These results suggest NF-Y is a central player in TSS selection in metazoans and highlight the deleterious consequences of inaccurate transcription initiation.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-10905-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10905-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-10905-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().