UBF levels determine the number of active ribosomal RNA genes in mammals

Elaine Sanij, Gretchen Poortinga, Kerith Sharkey, Sandy Hung, Timothy P. Holloway, Jaclyn Quin, Elysia Robb, Lee H. Wong, Walter G. Thomas, Victor Stefanovsky, Tom Moss, Lawrence Rothblum, Katherine M. Hannan, Grant A. McArthur, Richard B. Pearson, Ross D. Hannan

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117 Citations (Scopus)

Abstract

In mammals, the mechanisms regulating the number of active copies of the ∼200 ribosomal RNA (rRNA) genes transcribed by RNA polymerase I are unclear. We demonstrate that depletion of the transcription factor upstream binding factor (UBF) leads to the stable and reversible methylation-independent silencing of rRNA genes by promoting histone H1 - induced assembly of transcriptionally inactive chromatin. Chromatin remodeling is abrogated by the mutation of an extracellular signal-regulated kinase site within the high mobility group box 1 domain of UBF1, which is required for its ability to bend and loop DNA in vitro. Surprisingly, rRNA gene silencing does not reduce net rRNA synthesis as transcription from remaining active genes is increased. We also show that the active rRNA gene pool is not static but decreases during differentiation, correlating with diminished UBF expression. Thus, UBF1 levels regulate active rRNA gene chromatin during growth and differentiation.

Original languageEnglish
Pages (from-to)1259-1274
Number of pages16
JournalJournal of Cell Biology
Volume183
Issue number7
DOIs
Publication statusPublished - 29 Dec 2008

Cite this

Sanij, E., Poortinga, G., Sharkey, K., Hung, S., Holloway, T. P., Quin, J., ... Hannan, R. D. (2008). UBF levels determine the number of active ribosomal RNA genes in mammals. Journal of Cell Biology, 183(7), 1259-1274. https://doi.org/10.1083/jcb.200805146
Sanij, Elaine ; Poortinga, Gretchen ; Sharkey, Kerith ; Hung, Sandy ; Holloway, Timothy P. ; Quin, Jaclyn ; Robb, Elysia ; Wong, Lee H. ; Thomas, Walter G. ; Stefanovsky, Victor ; Moss, Tom ; Rothblum, Lawrence ; Hannan, Katherine M. ; McArthur, Grant A. ; Pearson, Richard B. ; Hannan, Ross D. / UBF levels determine the number of active ribosomal RNA genes in mammals. In: Journal of Cell Biology. 2008 ; Vol. 183, No. 7. pp. 1259-1274.
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abstract = "In mammals, the mechanisms regulating the number of active copies of the ∼200 ribosomal RNA (rRNA) genes transcribed by RNA polymerase I are unclear. We demonstrate that depletion of the transcription factor upstream binding factor (UBF) leads to the stable and reversible methylation-independent silencing of rRNA genes by promoting histone H1 - induced assembly of transcriptionally inactive chromatin. Chromatin remodeling is abrogated by the mutation of an extracellular signal-regulated kinase site within the high mobility group box 1 domain of UBF1, which is required for its ability to bend and loop DNA in vitro. Surprisingly, rRNA gene silencing does not reduce net rRNA synthesis as transcription from remaining active genes is increased. We also show that the active rRNA gene pool is not static but decreases during differentiation, correlating with diminished UBF expression. Thus, UBF1 levels regulate active rRNA gene chromatin during growth and differentiation.",
author = "Elaine Sanij and Gretchen Poortinga and Kerith Sharkey and Sandy Hung and Holloway, {Timothy P.} and Jaclyn Quin and Elysia Robb and Wong, {Lee H.} and Thomas, {Walter G.} and Victor Stefanovsky and Tom Moss and Lawrence Rothblum and Hannan, {Katherine M.} and McArthur, {Grant A.} and Pearson, {Richard B.} and Hannan, {Ross D.}",
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Sanij, E, Poortinga, G, Sharkey, K, Hung, S, Holloway, TP, Quin, J, Robb, E, Wong, LH, Thomas, WG, Stefanovsky, V, Moss, T, Rothblum, L, Hannan, KM, McArthur, GA, Pearson, RB & Hannan, RD 2008, 'UBF levels determine the number of active ribosomal RNA genes in mammals', Journal of Cell Biology, vol. 183, no. 7, pp. 1259-1274. https://doi.org/10.1083/jcb.200805146

UBF levels determine the number of active ribosomal RNA genes in mammals. / Sanij, Elaine; Poortinga, Gretchen; Sharkey, Kerith; Hung, Sandy; Holloway, Timothy P.; Quin, Jaclyn; Robb, Elysia; Wong, Lee H.; Thomas, Walter G.; Stefanovsky, Victor; Moss, Tom; Rothblum, Lawrence; Hannan, Katherine M.; McArthur, Grant A.; Pearson, Richard B.; Hannan, Ross D.

In: Journal of Cell Biology, Vol. 183, No. 7, 29.12.2008, p. 1259-1274.

Research output: Contribution to journalArticleResearchpeer-review

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Sanij E, Poortinga G, Sharkey K, Hung S, Holloway TP, Quin J et al. UBF levels determine the number of active ribosomal RNA genes in mammals. Journal of Cell Biology. 2008 Dec 29;183(7):1259-1274. https://doi.org/10.1083/jcb.200805146