Promoter proximal pausing on genes in metazoans

Gilmour, David S.

doi:10.1007/s00412-008-0182-4

Cited by 84 publications

(79 citation statements)

References 95 publications

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“…Progression of Pol II through these stages is modulated by the interplay of numerous factors. Of the various mechanisms that regulate transcription, promoter-proximal pausing during early elongation has recently gained recognition as a widespread rate-limiting step in metazoans (1,2). Genomewide analyses have revealed that thousands of genes in higher eukaryotes contain transcriptionally engaged Pol II concentrated at their promoters, indicating a postinitiation regulatory mechanism (3)(4)(5).…”

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confidence: 99%

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Interactions between DSIF (DRB sensitivity inducing factor), NELF (negative elongation factor), and the Drosophila RNA polymerase II transcription elongation complex

Missra

Gilmour

2010

Proc. Natl. Acad. Sci. U.S.A.

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Negative elongation factor (NELF) and 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole sensitivity-inducing factor (DSIF) are involved in pausing RNA Polymerase II (Pol II) in the promoter-proximal region of the hsp70 gene in Drosophila, before heat shock induction. Such blocks in elongation are widespread in the Drosophila genome. However, the mechanism by which DSIF and NELF participate in setting up the paused Pol II remains unclear. We analyzed the interactions among DSIF, NELF, and a reconstituted Drosophila Pol II elongation complex to gain insight into the mechanism of pausing. Our results show that DSIF and NELF require a nascent transcript longer than 18 nt to stably associate with the Pol II elongation complex. Protein-RNA cross-linking reveals that Spt5, the largest subunit of DSIF, contacts the nascent RNA as the RNA emerges from the elongation complex. Taken together, these results provide a possible model by which DSIF binds the elongation complex via association with the nascent transcript and subsequently recruits NELF. Although DSIF and NELF were both required for inhibition of transcription, we did not detect a NELF-RNA contact when the nascent transcript was between 22 and 31 nt long, which encompasses the region where promoter-proximal pausing occurs on many genes in Drosophila. This raises the possibility that RNA binding by NELF is not necessary in promoter-proximal pausing.transcriptional pausing | gene expression | negative elongation factors

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confidence: 99%

“…Another model, based on the sequence similarity between NELF-A and the hepatitis delta virus antigen posits that the NELF-A subunit associates with the clamp domain of Pol II (20,21). This association could alter the active site of the Pol II in a way that inhibits elongation (1).…”

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confidence: 99%

Interactions between DSIF (DRB sensitivity inducing factor), NELF (negative elongation factor), and the Drosophila RNA polymerase II transcription elongation complex

Missra

Gilmour

2010

Proc. Natl. Acad. Sci. U.S.A.

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132

137

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“…In active genes, gene-specific transcriptional activators participate in PIC assembly. In contrast, in inactive genes, the absence of gene-specific transcriptional activators or the presence of gene-specific transcriptional repressors prevents RNAP II recruitment and PIC assembly [6,7]. Thus, in oocytes, gene silencing might be attributable to the lack of RNAP II recruitment in any promoter regions.…”

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confidence: 99%

Global Gene Silencing is Caused by the Dissociation of RNA Polymerase II from DNA in Mouse Oocytes

Abe

Inoue

Suzuki

et al. 2010

Journal of Reproduction and Development

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Abstract. As mouse oocytes approach maturity, a global repression of gene transcription occurs. Here, we investigated the involvement of RPB1, the largest subunit of RNA polymerase II (RNAP II), in the regulation of this transcriptional silencing mechanism. Using BrUTP to follow transcription in an in vitro run-on assay, we observed an abrupt decrease in transcriptional activity when oocytes reached their full size (approximately 80 μm). Immunoblotting using antibodies specific for the phosphorylated and unphosphorylated forms of RPB1 revealed that RPB1 is phosphorylated at Ser-2 and Ser-5 in the small growing oocytes in which active transcription occurs. By contrast, in transcriptionally inactive, full-grown oocytes, RPB1 is predominantly unphosphorylated. When we permeabilized the nuclear membrane using Triton X-100 during fixation for immunocytochemistry, the unphosphorylated form of RPB1 diffused out of the nucleus in the full-grown oocytes but still remained there in the small growing oocytes, indicating that RPB1 is not bound to DNA in full-grown oocytes. These results suggest that the immediate cause of global transcriptional silencing is the dissociation of RNAP II from the DNA. We also observed dissociation of RPB1 from the DNA in fullgrown oocytes treated with trichostatin A to decondense their chromatin, suggesting that chromatin condensation is not an essential process in gene silencing during oocyte growth.

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“…70 Its presence was discovered initially in heat-shock genes, 71 but detailed RNAPII profiles show that it probably is a wide-spread phenomenon, 72,73 and serves as a regulatory check-point. 74,75 MOF has a peculiar chromatin binding profile that mirrors that of other MSLs i.e., found at the 3' end of the X chromosomal genes, but in addition is also found at the promoters of X chromosomal and other autosomal genes. 67 In the light of the results that come from roX mutants, 35,65 it might be the time to once again think of dosage compensation as an event that takes place at the promoters of target genes.…”

Section: Transcription or Sequence Or Both: An Integrative Modelmentioning

confidence: 92%

roX RNAs: Non-coding regulators of the male X chromosome in flies

Ilık

Akhtar²

2009

RNA Biology

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The roX RNAs represent one of the paradigm examples of large non-coding RNAs involved in chromatin regulation. Interestingly, roX genes have a dual life. The RNA product is part of the MSL complex required for dosage compensation of the male X chromosome in Drosophila while the genomic location is used as a binding platform for MSL complex assembly. In this review we discuss both aspects of roX function and propose an integrated model for possible mechanisms how these RNAs might be involved in epigenetic regulation of the male X chromosome.

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Promoter proximal pausing on genes in metazoans

Cited by 84 publications

References 95 publications

Interactions between DSIF (DRB sensitivity inducing factor), NELF (negative elongation factor), and the Drosophila RNA polymerase II transcription elongation complex

Interactions between DSIF (DRB sensitivity inducing factor), NELF (negative elongation factor), and the Drosophila RNA polymerase II transcription elongation complex

Global Gene Silencing is Caused by the Dissociation of RNA Polymerase II from DNA in Mouse Oocytes

roX RNAs: Non-coding regulators of the male X chromosome in flies

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