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In Vitro Transcription Assays and Their Application in Drug Discovery
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c-Myc regulates transcriptional pause release.

Peter B Rahl1, Charles Y Lin, Amy C Seila

  • 1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Cell
|May 4, 2010
PubMed
Summary

Promoter-proximal pausing is a general transcription step in mammalian cells, offering a new regulatory point for gene expression. The transcription factor c-Myc specifically promotes the release of RNA polymerase II from these pauses.

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Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Cancer Biology

Background:

  • Transcription initiation by RNA polymerase II (Pol II) at promoters is a critical gene expression regulatory step.
  • Specific DNA-binding transcription factors mediate the recruitment of the Pol II transcription apparatus.
  • The role of transcription factors in regulating Pol II activity beyond initial recruitment is an area of active investigation.

Purpose of the Study:

  • To investigate promoter-proximal pausing as a general regulatory mechanism for Pol II transcription in mammalian cells.
  • To determine the specific roles of transcription factors in Pol II recruitment versus pause release.
  • To elucidate the function of the transcription factor c-Myc in the context of Pol II transcription regulation.

Main Methods:

  • Analysis of RNA polymerase II transcription dynamics in mammalian cells.
  • Investigating the interaction of transcription factors with Pol II at target gene promoters.
  • Utilizing techniques to differentiate between Pol II recruitment and pause release mechanisms.

Main Results:

  • Promoter-proximal pausing is identified as a widespread feature of Pol II transcription in mammalian cells.
  • Transcription factors can be categorized by their role in either Pol II recruitment or promoter-proximal pause release.
  • The transcription factor c-Myc primarily functions in promoting Pol II pause release at its target genes, not recruitment.

Conclusions:

  • Promoter-proximal pausing represents a significant, previously underappreciated regulatory checkpoint in gene expression.
  • The distinct roles of transcription factors in recruitment and pause release provide a more nuanced understanding of gene regulation.
  • c-Myc's role in Pol II pause release has critical implications for understanding its amplification in human cancers.