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Promoter‐proximal pausing of Pol II enhances gene expression
Author(s) -
Adelman Karen,
Gilchrist Daniel,
Nechaev Sergei,
Dos Santos Gilberto
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.316.2
Subject(s) - rna polymerase ii , promoter , transcription (linguistics) , chromatin , gene , biology , gene expression , regulation of gene expression , rna polymerase iii , nucleosome , microbiology and biotechnology , genetics , rna , rna polymerase , linguistics , philosophy
Recent work from our lab and others has revealed that many genes in higher eukaryotes are regulated at a step after recruitment of RNA polymerase II (Pol II) to a gene's promoter. In particular, we have found that Pol II initiates transcription and then pauses during early elongation of Drosophila genes that are involved in development or the response to environmental signals. Release of this promoter‐proximally paused Pol II occurs quickly upon gene activation, allowing for a rapid induction of transcription. As described below, we have discovered that in addition to facilitating rapid gene activation, promoter‐proximally paused Pol II can enhance both basal and induced gene expression by maintaining a permissive chromatin architecture around a gene's promoter. The Negative Elongation Factor (NELF) is a transcription regulatory complex that induces pausing of Pol II during early transcription elongation. We report that RNAi against NELF decreases promoter‐proximally paused Pol II and, surprisingly, that knock‐down of this "negative" factor has largely negative effects on gene expression. Investigation of the down‐regulated promoters shows that significant loss of Pol II pausing is accompanied by increased nucleosome occupancy of the promoter region. These results indicate a dynamic, antagonistic relationship between paused Pol II and nucleosomes, and reveal a mechanism through which paused Pol II can poise a gene for further or future induction.

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