Ready, pause, go: regulation of RNA polymerase II pausing and release by cellular signaling pathways

Liu, Xiuli; Kraus, W. Lee; Bai, Xiaoying

doi:10.1016/j.tibs.2015.07.003

Cited by 137 publications

(119 citation statements)

References 108 publications

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“…Genome-wide studies have demonstrated that promoter proximal Pol II pausing is common and that increased transcription from these genes results from release of the paused Pol II and increased elongation (40,41). It is proposed that promoter paused Pol II favors a synchronized response to environmental stimuli (42).…”

Section: Discussionmentioning

confidence: 99%

The C/ebp-Atf response element (CARE) location reveals two distinct Atf4-dependent, elongation-mediated mechanisms for transcriptional induction of aminoacyl-tRNA synthetase genes in response to amino acid limitation

et al. 2016

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The response to amino acid (AA) limitation of the entire aminoacyl-tRNA synthetase (ARS) gene family revealed that 16/20 of the genes encoding cytoplasmic-localized enzymes are transcriptionally induced by activating transcription factor 4 (Atf4) via C/ebp-Atf-Response-Element (CARE) enhancers. In contrast, only 4/19 of the genes encoding mitochondrial-localized ARSs were weakly induced. Most of the activated genes have a functional CARE near the transcription start site (TSS), but for others the CARE is downstream. Regardless of the location of CARE enhancer, for all ARS genes there was constitutive association of RNA polymerase II (Pol II) and the general transcription machinery near the TSS. However, for those genes with a downstream CARE, Atf4, C/ebp-homology protein (Chop), Pol II and TATA-binding protein exhibited enhanced recruitment to the CARE during AA limitation. Increased Atf4 binding regulated the association of elongation factors at both the promoter and the enhancer regions, and inhibition of cyclin-dependent kinase 9 (CDK9), that regulates these elongation factors, blocked induction of the AA-responsive ARS genes. Protein pull-down assays indicated that Atf4 directly interacts with CDK9 and its associated protein cyclin T1. The results demonstrate that AA availability modulates the ARS gene family through modulation of transcription elongation.

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Section: Discussionmentioning

confidence: 99%

The C/ebp-Atf response element (CARE) location reveals two distinct Atf4-dependent, elongation-mediated mechanisms for transcriptional induction of aminoacyl-tRNA synthetase genes in response to amino acid limitation

et al. 2016

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“…G4 formation may be favored by formation of an R-loop on the C strand (Fragkos et al 2015), and G4/OGRE elements could function as a structural switch: folded or unfolded. Alternatively, replication origins could be activated at pre-RCs and then transiently stall at the proximal G4 on the leading strand, a phenomenon similar to transcriptional pausing (Liu et al 2015). This mechanism could be used to start initiation on the opposite strand, similarly to the model proposed for the DBF4 replication origin (Romero and Lee 2008).…”

Section: G-rich or G4 Signatures At Replication Origins And Nucleosommentioning

confidence: 97%

The chromatin environment shapes DNA replication origin organization and defines origin classes

et al. 2015

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To unveil the still-elusive nature of metazoan replication origins, we identified them genome-wide and at unprecedented high-resolution in mouse ES cells. This allowed initiation sites (IS) and initiation zones (IZ) to be differentiated. We then characterized their genetic signatures and organization and integrated these data with 43 chromatin marks and factors. Our results reveal that replication origins can be grouped into three main classes with distinct organization, chromatin environment, and sequence motifs. Class 1 contains relatively isolated, low-efficiency origins that are poor in epigenetic marks and are enriched in an asymmetric AC repeat at the initiation site. Late origins are mainly found in this class. Class 2 origins are particularly rich in enhancer elements. Class 3 origins are the most efficient and are associated with open chromatin and polycomb protein-enriched regions. The presence of Origin G-rich Repeated elements (OGRE) potentially forming G-quadruplexes (G4) was confirmed at most origins. These coincide with nucleosome-depleted regions located upstream of the initiation sites, which are associated with a labile nucleosome containing H3K64ac. These data demonstrate that specific chromatin landscapes and combinations of specific signatures regulate origin localization. They explain the frequently observed links between DNA replication and transcription. They also emphasize the plasticity of metazoan replication origins and suggest that in multicellular eukaryotes, the combination of distinct genetic features and chromatin configurations act in synergy to define and adapt the origin profile.

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“…The pausing of Pol II 20–60 bp into the transcription unit poises genes for rapid induction in response to external stimuli and maintains promoter-proximal regions in a nucleosome-depleted state [54]. The transcription elongation factor DSIF (human ortholog of the yeast Spt4–Spt5 complex) acts in concert with another protein complex, NELF, to establish promoter-proximal pausing of Pol II [55] (Figure 2). Release from pausing is triggered by phosphorylation of NELF and Spt5 by P-TEFb (CDK9-cyclin T complex), upon which NELF dissociates from the polymerase and DSIF becomes a positive elongation factor [55].…”

Section: Paf1c Regulates Gene Expression Through Diverse Mechanismsmentioning

confidence: 99%

Emerging Insights into the Roles of the Paf1 Complex in Gene Regulation

Oss

Cucinotta

Arndt

2017

Trends in Biochemical Sciences

147

130

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The conserved, multifunctional Paf1 complex (Paf1C) regulates all stages of the RNA polymerase II transcription cycle. In this review, we examine a diverse set of recent studies from various organisms that build on foundational studies in budding yeast. These studies identify new roles for Paf1C in the control of gene expression and the regulation of chromatin structure. In exploring these advances, we find that Paf1C’s various functions, such as the regulation of promoter-proximal pausing and development in higher eukaryotes, are complex and context-dependent. As more becomes known about the role of Paf1C in human disease, interest in the molecular mechanisms underpinning Paf1C function will continue to increase.

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Ready, pause, go: regulation of RNA polymerase II pausing and release by cellular signaling pathways

Cited by 137 publications

References 108 publications

The C/ebp-Atf response element (CARE) location reveals two distinct Atf4-dependent, elongation-mediated mechanisms for transcriptional induction of aminoacyl-tRNA synthetase genes in response to amino acid limitation

The C/ebp-Atf response element (CARE) location reveals two distinct Atf4-dependent, elongation-mediated mechanisms for transcriptional induction of aminoacyl-tRNA synthetase genes in response to amino acid limitation

The chromatin environment shapes DNA replication origin organization and defines origin classes

Emerging Insights into the Roles of the Paf1 Complex in Gene Regulation

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