c-Myc regulates transcriptional pause release

By P. Rahl, Charles Y. Lin, A. C. Seila, Ryan A. Flynn, Scott Mccuine, C. Burge, Phillip A. Sharp, Richard A. Young. Cell, 2010

1,316 citations recorded by the source corpus.

Recruitment of the RNA Polymerase II (Pol II) transcription initiation apparatus to promoters by specific DNA binding transcription factors is well recognized as a key regulatory step in gene expression. We report here that promoter-proximal pausing is a general feature of transcription by Pol II in mammalian cells, and thus an additional step where regulation of gene expression occurs. This suggests that some transcription factors recruit the transcription apparatus to promoters, while others effect promoter-proximal pause release. Indeed, we find that the transcription factor c-Myc, a key regulator of cellular proliferation, plays a major role in Pol II pause release rather than Pol II recruitment at its target genes. We discuss the implications of these results for the role of c-Myc amplification in human cancer.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/baac1c9c5b1d67654799e0bc9915881220d72bc6

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Citations in the corpus

The RNA polymerase II CTD coordinates transcription and RNA processing. (2012, background): “Although a general model outlines changes in CTD phosphorylation along the length of transcribed genes, how common is regulated CTD modification in control of specific genes, and how is this achieved? A well-documented example is recruitment of P-TEFb by the oncogenic transcription factor c-Myc (Ebe”
CpG islands and the regulation of transcription. (2011, neutral): “A study of chromatin at LPS-inducible genes in macrophages found that CGIs are relatively nucleosome-deficient (Ramirez-Carrozzi et al. 2009).”
Parsing the interferon transcriptional network and its disease associations (2016, neutral): “(2013) and sequenced; for PolII and Stat1, 2 ChIPseq per (Rahl et al., 2010) and sequenced (Table S2A).”
The Transcriptional and Epigenomic Foundations of Ground State Pluripotency (2012, methodology): “c-Myc is implicated in Pol II pause release (Rahl et al., 2010).”
Charting histone modifications and the functional organization of mammalian genomes (2011, background): “Indeed, recent studies in macrophages and ES cells have documented roles for specific transcription factors in regulating steps downstream of initiatio”
Transcriptional Regulation by Hypoxia Inducible Factors (2013, background): “This phenomenon appears to be widespread, and has been demonstrated for other stimulus-responsive transcription programs (Espinosa, 2010; Gilchrist et al., 2008; Rahl et al., 2010).”
Transcriptional Amplification in Tumor Cells with Elevated c-Myc (2012, positive): “Chromatin Immunoprecipitation ChIP was carried out as described in Rahl et al. (2010).”
MYC on the Path to Cancer (2012, background): “A subsequent study examines the role of Myc in transcription and relief of RNA polymerase (Pol) II paused complexes (Rahl et al., 2010).”
m6A RNA modification controls cell fate transition in mammalian embryonic stem cells (2014, methodology): “Mouse Pol II occupancy data, mRNA half life and Protein translation efficiency were obtained from (Ingolia et al., 2011; Rahl et al., 2010; Sharova et al., 2009).”
Transcriptional Regulation and its Misregulation in Disease (2013, neutral): “Transcription factors can be separated into two classes based on their regulatory responsibilities: control of initiation versus control of elongation (Adelman and Lis, 2012; Fuda et al., 2009; Rahl et al., 2010; Yankulov et al., 1994; Zhou et al., 2012b).”