Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/96298
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Type: Journal article
Title: A novel role for the Pol I transcription factor UBTF in maintaining genome stability through the regulation of highly transcribed Pol II genes
Author: Sanij, E.
Diesch, J.
Lesmana, A.
Poortinga, G.
Lidgerwood, G.
Hein, N.
Cameron, D.
Ellul, J.
Goodall, G.
Wong, L.
Dhillon, A.
Hamdane, N.
Rothblum, L.
Pearson, R.
Haviv, I.
Moss, T.
Hannan, R.
Citation: Genome Research, 2015; 25(2):201-212
Publisher: CSH Press
Issue Date: 2015
ISSN: 1088-9051
1549-5469
Statement of
Responsibility: 
Elaine Sanij, Jeannine Diesch, Analia Lesmana, Gretchen Poortinga, Nadine Hein, Grace Lidgerwood, Donald P. Cameron, Jason Ellul, Gregory J. Goodall, Lee H. Wong, Amardeep S. Dhillon, Nourdine Hamdane, Lawrence I. Rothblum, Richard B. Pearson, Izhak Haviv, Tom Moss, and Ross D. Hannan
Abstract: Mechanisms to coordinate programs of highly transcribed genes required for cellular homeostasis and growth are unclear. Upstream binding transcription factor 1 (UBTF, also called UBF) is thought to function exclusively in RNA polymerase I (Pol I)-specific transcription of the ribosomal genes. Here we report that, the two isoforms of UBTF (UBTF1/2) are also enriched at highly expressed Pol II-transcribed genes throughout the mouse genome. Further analysis of UBTF1/2 DNA binding in immortalised human epithelial cells and their isogenically matched transformed counterparts reveals an additional repertoire of UBTF1/2-bound genes involved in the regulation of cell cycle checkpoints and DNA damage response. As proof of a functional role for UBTF1/2 in regulating Pol II transcription, we demonstrate that UBTF1/2 is required for recruiting Pol II to the highly transcribed histone gene clusters and for their optimal expression. Intriguingly, lack of UBTF1/2 does not affect chromatin marks or nucleosome density at histone genes. Instead it results in increased accessibility of the histone promoters and transcribed regions to micrococcal nuclease, implicating UBTF1/2 in mediating DNA accessibility. Unexpectedly, UBTF2, which does not function in Pol I transcription, is sufficient to regulate histone gene expression in the absence of UBTF1. Moreover, depletion of UBTF1/2 and subsequent reduction in histone gene expression is associated with DNA damage and genomic instability independent of Pol I transcription. Thus, we have uncovered a novel role for UBTF1 and UBTF2 in maintaining genome stability through coordinating the expression of highly transcribed Pol I (UBTF1 activity) and Pol II genes (UBTF2 activity).
Keywords: Cell Line, Transformed
NIH 3T3 Cells
Chromatin
Nucleosomes
Animals
Humans
Mice
DNA Damage
Genomic Instability
RNA Polymerase I
RNA Polymerase II
Pol1 Transcription Initiation Complex Proteins
Histones
Chromatin Immunoprecipitation
Computational Biology
Transcription, Genetic
Gene Expression Regulation
Binding Sites
Protein Binding
Multigene Family
Transcription Initiation Site
Gene Knockdown Techniques
High-Throughput Nucleotide Sequencing
Rights: © 2015 Sanij et al. This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
DOI: 10.1101/gr.176115.114
Appears in Collections:Aurora harvest 3
Medicine publications

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