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NF-Y controls fidelity of transcription initiation at gene promoters through maintenance of the nucleosome-depleted region
- Source :
- Nature Communications, Nature Communications, Nature Publishing Group, 2019, 10 (1), pp.3072. ⟨10.1038/s41467-019-10905-7⟩
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
Abstract
- International audience; 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.
- Subjects :
- Site Transcription Initiation
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Small Interfering
[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]
Chromatin
Nucleosomes
Promoter Regions
Mice
Metabolism
CCAAT-Binding Factor
Gene Knockdown Techniques
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
RNA
Transcription Initiation Site
[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
Embryonic Stem Cells
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications, Nature Communications, Nature Publishing Group, 2019, 10 (1), pp.3072. ⟨10.1038/s41467-019-10905-7⟩
- Accession number :
- edsair.dedup.wf.001..bb944bd98ad0d69d7992613715e407be