A unified view of the sequence and functional organization of the human RNA polymerase II promoter

被引:29
|
作者
Luse, Donal S. [1 ]
Parida, Mrutyunjaya [2 ]
Spector, Benjamin M. [2 ]
Nilson, Kyle A. [2 ,3 ]
Price, David H. [2 ]
机构
[1] Cleveland Clin, Dept Cardiovasc & Metab Sci, Lerner Res Inst, Cleveland, OH 44195 USA
[2] Univ Iowa, Dept Biochem, Iowa City, IA 52242 USA
[3] Penn State Univ, Dept Biochem & Mol Biol, Ctr Eukaryot Gene Regulat, University Pk, PA 16802 USA
基金
美国国家卫生研究院;
关键词
PRE-INITIATION COMPLEX; TRANSCRIPTION; CHROMATIN; BINDING; DNA; NUCLEOSOMES; DYNAMICS; DISTINCT; DOWNSTREAM; NUCLEASE;
D O I
10.1093/nar/gkaa531
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To better understand human RNA polymerase II (Pol II) promoters in the context of promoter-proximal pausing and local chromatin organization, 5' and 3' ends of nascent capped transcripts and the locations of nearby nucleosomes were accurately identified through sequencing at exceptional depth. High quality visualization tools revealed a preferred sequence that defines over 177 000 core promoters with strengths varying by >10 000-fold. This sequence signature encompasses and better defines the binding site for TFIID and is surprisingly invariant over a wide range of promoter strength. We identified a sequence motif associated with promoter-proximal pausing and demonstrated that cap methylation only begins once transcripts are about 30 nt long. Mapping also revealed a similar to 150 bp periodic downstream sequence element (PDE) following the typical pause location, strongly suggestive of a +1 nucleosome positioning element. A nuclear run-off assay utilizing the unique properties of the DNA fragmentation factor (DFF) coupled with sequencing of DFF protected fragments demonstrated that a +1 nucleosome is present downstream of paused Pol II. Our data more clearly define the human Pol II promoter: a TFIID binding site with built-in downstream information directing ubiquitous promoter-proximal pausing and downstream nucleosome location.
引用
收藏
页码:7767 / 7785
页数:19
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