A positioned +1 nucleosome enhances promoter-proximal pausing
|Author/s||Jimeno González, Silvia
Ceballos Chávez, María
Reyes , José Carlos
|Department||Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER)|
|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) ...
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.
|Funding agencies||Ministerio de Economía y Competitividad (MINECO). España|
|Citation||Jimeno González, S., Ceballos Chávez, M. y Reyes , J.C. (2015). A positioned +1 nucleosome enhances promoter-proximal pausing. Nucleic Acids Research, 43 (6), 3068-3078.|