A positioned +1 nucleosome enhances promoter-proximal pausing

Nucleic Acids Research
Silvia Jimeno-GonzálezJosé C Reyes

Abstract

Chromatin distribution is not uniform along the human genome. In most genes there is a promoter-associated nucleosome free region (NFR) followed by an array of nucleosomes towards the gene body in which the first (+1) nucleosome is strongly positioned. The function of this characteristic chromatin distribution in transcription is not fully understood. Here we show in vivo that the +1 nucleosome plays a role in modulating RNA polymerase II (RNAPII) promoter-proximal pausing. When a +1 nucleosome is strongly positioned, elongating RNAPII has a tendency to stall at the promoter-proximal region, recruits more negative elongation factor (NELF) and produces less mRNA. The nucleosome-induced pause favors pre-mRNA quality control by promoting the addition of the cap to the nascent RNA. Moreover, the uncapped RNAs produced in the absence of a positioned nucleosome are degraded by the 5'-3' exonuclease XRN2. Interestingly, reducing the levels of the chromatin remodeler ISWI factor SNF2H decreases +1 nucleosome positioning and increases RNAPII pause release. This work demonstrates a function for +1 nucleosome in regulation of transcription elongation, pre-mRNA processing and gene expression.

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Citations

Aug 25, 2015·FEBS Letters·Nicolás Nieto MorenoAlberto R Kornblihtt
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Apr 15, 2021·Cell Reports·Andrés Herrero-RuizFelipe Cortés-Ledesma

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Methods Mentioned

BETA
nuclease assay
immunoprecipitation
RNA-IP
ChIP
ChIPs
footprinting

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