TRIM28 as a novel transcriptional elongation factor

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Abstract

TRIM28 is a multidomain protein with versatile functions in transcription and DNA repair. Recently it was shown that this factor plays unanticipated roles in transcriptional elongation. TRIM28 was shown to stabilize the pausing of RNA polymerase II (Pol II) close to the transcriptional start site in many unactivated genes, permitting Pol II accumulation and readying genes for induction. In addition, the factor was shown to respond rapidly to signals accompanying transcriptional activation permitting the productive elongation of RNA by previously paused Pol II. We discuss here critical regulatory mechanisms of TRIM28 in transcriptional control and DNA repair that may illuminate the novel roles of this factor in pausing and elongation of Pol II.

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Most cited references 49

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Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans.

Karen Adelman, John Lis (2012)

Recent years have witnessed a sea change in our understanding of transcription regulation: whereas traditional models focused solely on the events that brought RNA polymerase II (Pol II) to a gene promoter to initiate RNA synthesis, emerging evidence points to the pausing of Pol II during early elongation as a widespread regulatory mechanism in higher eukaryotes. Current data indicate that pausing is particularly enriched at genes in signal-responsive pathways. Here the evidence for pausing of Pol II from recent high-throughput studies will be discussed, as well as the potential interconnected functions of promoter-proximally paused Pol II.

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Getting up to speed with transcription elongation by RNA polymerase II.

Iris Jonkers, John Lis (2015)

Recent advances in sequencing techniques that measure nascent transcripts and that reveal the positioning of RNA polymerase II (Pol II) have shown that the pausing of Pol II in promoter-proximal regions and its release to initiate a phase of productive elongation are key steps in transcription regulation. Moreover, after the release of Pol II from the promoter-proximal region, elongation rates are highly dynamic throughout the transcription of a gene, and vary on a gene-by-gene basis. Interestingly, Pol II elongation rates affect co-transcriptional processes such as splicing, termination and genome stability. Increasing numbers of factors and regulatory mechanisms have been associated with the steps of transcription elongation by Pol II, revealing that elongation is a highly complex process. Elongation is thus now recognized as a key phase in the regulation of transcription by Pol II.

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The Mediator complex: a central integrator of transcription.

Benjamin Allen, Dylan J. Taatjes (2015)

The RNA polymerase II (Pol II) enzyme transcribes all protein-coding and most non-coding RNA genes and is globally regulated by Mediator - a large, conformationally flexible protein complex with a variable subunit composition (for example, a four-subunit cyclin-dependent kinase 8 module can reversibly associate with it). These biochemical characteristics are fundamentally important for Mediator's ability to control various processes that are important for transcription, including the organization of chromatin architecture and the regulation of Pol II pre-initiation, initiation, re-initiation, pausing and elongation. Although Mediator exists in all eukaryotes, a variety of Mediator functions seem to be specific to metazoans, which is indicative of more diverse regulatory requirements.

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Author and article information

Contributors

Heeyoun Bunch: hbunch@bidmc.harvard.edu

Stuart K Calderwood:

ORCID: http://orcid.org/0000-0003-1708-1137

scalderw@bidmc.harvard.edu

Journal

Journal ID (nlm-ta): BMC Mol Biol

Journal ID (iso-abbrev): BMC Mol. Biol

Title: BMC Molecular Biology

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2199

Publication date (Electronic): 21 August 2015

Publication date PMC-release: 21 August 2015

Publication date Collection: 2015

Volume: 16

Electronic Location Identifier: 14

Affiliations

Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Center for Life Sciences, 3 Blackfan circle, Boston, MA 02115 USA

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Stuart K Calderwood http://orcid.org/0000-0003-1708-1137

Article

Publisher ID: 40

DOI: 10.1186/s12867-015-0040-x

PMC ID: 4545989

PubMed ID: 26293668

SO-VID: 34fd7cc2-66e0-4fed-b71e-2462acfa1de6

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Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 10 April 2015

Date accepted : 22 May 2015

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ScienceOpen disciplines: Molecular biology

Keywords: tripartate 28,regulation,transcription,elongation,phosophorylation

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ScienceOpen disciplines: Molecular biology

Keywords: tripartate 28, regulation, transcription, elongation, phosophorylation

TRIM28 as a novel transcriptional elongation factor

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Abstract

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Most cited references 49

Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans.

Getting up to speed with transcription elongation by RNA polymerase II.

The Mediator complex: a central integrator of transcription.

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