A positioned +1 nucleosome enhances promoter-proximal pausing.
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.
Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas (CSIC), E-41012, Seville, Spain jose.reyes@cabimer.es.
Silvia
S
Jimeno-González
Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas (CSIC), E-41012, Seville, Spain.
María
M
Ceballos-Chávez
Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas (CSIC), E-41012, Seville, Spain jose.reyes@cabimer.es.
José C
JC
Reyes
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D005095:Exoribonucleases / Q000378:metabolism; D016259:Genes, myc; D015894:Genome, Human; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012315:RNA Caps / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D009707:Nucleosomes; D012315:RNA Caps; D012333:RNA, Messenger; D014157:Transcription Factors; C118437:negative elongation factor; D012319:RNA Polymerase II; D005095:Exoribonucleases; C120903:XRN2 protein, human; D000251:Adenosine Triphosphatases; C409462:SMARCA5 protein, human