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


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.

SUBMITTER: Oldfield AJ 

PROVIDER: S-EPMC6624317 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Oldfield Andrew J AJ   Henriques Telmo T   Kumar Dhirendra D   Burkholder Adam B AB   Cinghu Senthilkumar S   Paulet Damien D   Bennett Brian D BD   Yang Pengyi P   Scruggs Benjamin S BS   Lavender Christopher A CA   Rivals Eric E   Adelman Karen K   Jothi Raja R  

Nature communications 20190711 1


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 prot  ...[more]

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