NF-Y controls fidelity of transcription initiation at gene promoters through maintenance of the nucleosome-depleted region - LIRMM - Laboratoire d’Informatique, de Robotique et de Microélectronique de Montpellier Access content directly
Journal Articles Nature Communications Year : 2019

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

La protéine NF-Y contrôle la fidelité de l'initiation de la transcription aux promoteurs de gènes à travers la maintenance de région déplétée en nucléosome.

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.
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lirmm-02383488 , version 1 (27-11-2019)

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Andrew Oldfield, Telmo Henriques, Dhirendra Kumar, Adam B Burkholder, Senthilkumar Cinghu, et al.. NF-Y controls fidelity of transcription initiation at gene promoters through maintenance of the nucleosome-depleted region. Nature Communications, 2019, 10 (1), pp.3072. ⟨10.1038/s41467-019-10905-7⟩. ⟨lirmm-02383488⟩
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