Transcriptional pause, arrest and termination sites for RNA polymerase II in mammalian N- and c-mycgenes

Keene, Richard G.; Mueller, A.G.; Landick, Robert; London, Lucille

doi:10.1093/nar/27.15.3173

Cited by 39 publications

(38 citation statements)

References 43 publications

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“…Intrinsic elements in the DNA sequence can induce destabilizing secondary conformations in the nascent RNA and result in polymerase II pause, arrest, or termination without other intervening factors (24). In other studies, DNase hypersensitivity sites have been mapped to the attenuation site, together with DNA-binding proteins that presumably hinder transcript elongation (12,42), and the relief of attenuation correlates with loss of hypersensitivity sites.…”

Section: Discussionmentioning

confidence: 99%

Regulation of RelB Expression during the Initiation of Dendritic Cell Differentiation

Cejas

Carlson

Kolonias

et al. 2005

Molecular and Cellular Biology

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The transcription factor RelB is required for proper development and function of dendritic cells (DCs), and its expression is upregulated early during differentiation from a variety of progenitors. We explored this mechanism of upregulation in the KG1 cell line model of a DC progenitor and in the differentiation-resistant KG1a subline. RelB expression is relatively higher in untreated KG1a cells but is upregulated only during differentiation of KG1 by an early enhancement of transcriptional elongation, followed by an increase in transcription initiation. Restoration of protein kinase C␤II (PKC␤II) expression in KG1a cells allows them to differentiate into DCs. We show that PKC␤II also downregulated constitutive expression of NF-B in KG1a-transfected cells and restores the upregulation of RelB during differentiation by increased transcriptional initiation and elongation. The two mechanisms are independent and sensitive to PKC signaling levels. Conversely, RelB upregulation was inhibited in primary human monocytes where PKC␤II expression was knocked down by small interfering RNA targeting. Altogether, the data show that RelB expression during DC differentiation is controlled by PKC␤II-mediated regulation of transcriptional initiation and elongation.Dendritic cells (DCs) constitute a heterogeneous population of professional antigen-presenting cells with a unique role in the activation of naive T lymphocytes and the establishment of immunological tolerance and memory (2, 3). Their central role as regulators of the immune response has led to the examination of the underlying intracellular signaling pathways and gene expression that may regulate the differentiation of precursors into DCs (21, 60), most notably, the Rel/NF-B family of transcription factors (41, 61).NF-B exists in mammals as a homodimer or heterodimer of the Rel proteins NFB1 (p50/p105), NFB2 (p52/p100), c-Rel, RelA (p65), and RelB. The dimer can be sequestered in the cytoplasm by the inhibitory IBs, which in the canonical activation pathway can be phosphorylated, ubiquitinated, and degraded by the proteasome to allow the nuclear translocation of NF-B and activate transcription (63). On the other hand, the NF-B2 precursor form p100 can inhibit directly the nuclear translocation of heterodimers due to their IB-like ankyrin repeats and is activated by an alternative pathway that requires the NF-B-inducing kinase (NIK) and IKK␣ (62). In this pathway, the bound precursor p100 is processed in a regulated fashion to the p52 form to allow translocation to the nucleus. The p105 subunit also contains IB-like ankyrin repeats that could sequester NF-B dimers in the cytoplasm. However, its processing to the p50 form is constitutive (22,30).Overexpression of IB in mature DCs downregulates major histocompatibility complex (MHC) class II; the costimulatory molecules CD80, CD86, and CD40; and the proinflammatory cytokine tumor necrosis factor alpha (TNF-␣), indicating that antigen presentation is dependent on NF-B function (64). Likewise, the inhibitory p100 precursor ...

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Section: Discussionmentioning

confidence: 99%

Regulation of RelB Expression during the Initiation of Dendritic Cell Differentiation

Cejas

Carlson

Kolonias

et al. 2005

Molecular and Cellular Biology

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“…Transcriptional pause sites in c-MYC are amongst the best characterized of those in mammalian RNA polymerase II transcription units (Bentley and Groudine, 1986;Chung et al, 1987;Kerppola and Kane, 1988;Strobl and Eick, 1992;Keene et al, 1999). There is no obvious correlation between the single nucleotide mutations detected in the c-MYC exon 1 and the major polymerase II pausing/ termination site described in this exon.…”

Section: Discussionmentioning

confidence: 99%

The c-MYC allele that is translocated into the IgH locus undergoes constitutive hypermutation in a Burkitt's lymphoma line

Bemark

Neuberger

2000

Oncogene

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“…1991), between closely spaced genes (Ashfield et al 1991), and at several internal sites in the c and N-myc genes (Keene et al 1999). Artificial arrests (ARTAR) to pol II elongation have been created and shown to be effective in pausing pol II at positions far downstream from the promoter (Kulish and Struhl 2001).…”

Section: Pauses To Pol II Elongation Affect Splicingmentioning

confidence: 99%

Multiple links between transcription and splicing

Kornblihtt¹,

Mata²,

Fededa³

et al. 2004

RNA

428

385

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Transcription and pre-mRNA splicing are extremely complex multimolecular processes that involve protein-DNA, protein-RNA, and protein-protein interactions. Splicing occurs in the close vicinity of genes and is frequently cotranscriptional. This is consistent with evidence that both processes are coordinated and, in some cases, functionally coupled. This review focuses on the roles of cis-and trans-acting factors that regulate transcription, on constitutive and alternative splicing. We also discuss possible functions in splicing of the C-terminal domain (CTD) of the RNA polymerase II (pol II) largest subunit, whose participation in other key pre-mRNA processing reactions (capping and cleavage/polyadenylation) is well documented. Recent evidence indicates that transcriptional elongation and splicing can be influenced reciprocally: Elongation rates control alternative splicing and splicing factors can, in turn, modulate pol II elongation. The presence of transcription factors in the spliceosome and the existence of proteins, such as the coactivator PGC-1, with dual activities in splicing and transcription can explain the links between both processes and add a new level of complexity to the regulation of gene expression in eukaryotes.

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Transcriptional pause, arrest and termination sites for RNA polymerase II in mammalian N- and c-mycgenes

Cited by 39 publications

References 43 publications

Regulation of RelB Expression during the Initiation of Dendritic Cell Differentiation

Regulation of RelB Expression during the Initiation of Dendritic Cell Differentiation

The c-MYC allele that is translocated into the IgH locus undergoes constitutive hypermutation in a Burkitt's lymphoma line

Multiple links between transcription and splicing

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