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NF-Y controls fidelity of transcription initiation at gene promoters through maintenance of the nucleosome-depleted region
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.
Cited literature [77 references]
https://hal-lirmm.ccsd.cnrs.fr/lirmm-02383488
Contributor : Eric Rivals Connect in order to contact the contributor
Submitted on : Wednesday, November 27, 2019 - 5:33:41 PM
Last modification on : Monday, October 11, 2021 - 1:24:09 PM
Contributor : Eric Rivals Connect in order to contact the contributor
Submitted on : Wednesday, November 27, 2019 - 5:33:41 PM
Last modification on : Monday, October 11, 2021 - 1:24:09 PM
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2019-nat-com-Oldfield-etal-NF-...
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