RT Journal Article
SR Electronic
T1 NF-Y controls fidelity of transcription initiation at gene promoters through maintenance of the nucleosome-depleted region
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 369389
DO 10.1101/369389
A1 Andrew J Oldfield
A1 Telmo Henriques
A1 Dhirendra Kumar
A1 Adam B. Burkholder
A1 Senthilkumar Cinghu
A1 Damien Paulet
A1 Brian Bennett
A1 Pengyi Yang
A1 Benjamin S. Scruggs
A1 Christopher A. Lavender
A1 Eric Rivals
A1 Karen Adelman
A1 Raja Jothi
YR 2019
UL http://biorxiv.org/content/early/2019/05/02/369389.abstract
AB 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. 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 preinitiation complex and ectopic transcription initiation. Further, this phenomenon generates aberrant extended transcripts that undergo translation, disrupting gene expression profiles. These results establish NF-Y as a central player in TSS selection in metazoans and highlight the deleterious consequences of inaccurate transcription initiation.