Mitotic occupancy and lineage-specific transcriptional control of rRNA genes by Runx2

Daniel W. Young, Mohammad Q. Hassan, Jitesh Pratap, Mario Galindo, Sayyed K. Zaidi, Suk Hee Lee, Xiaoqing Yang, Ronglin Xie, Amjad Javed, Jean M. Underwood, Paul Furcinitti, Anthony N. Imbalzano, Sheldon Penman, Jeffrey A. Nickerson, Martin A. Montecino, Jane B. Lian, Janet L. Stein, Andre J van Wijnen, Gary S. Stein

Research output: Contribution to journalArticle

167 Citations (Scopus)

Abstract

Regulation of ribosomal RNA genes is a fundamental process that supports the growth of cells and is tightly coupled with cell differentiation. Although rRNA transcriptional control by RNA polymerase I (Pol I) and associated factors is well studied, the lineage-specific mechanisms governing rRNA expression remain elusive. Runt-related transcription factors Runx1, Runx2 and Runx3 establish and maintain cell identity, and convey phenotypic information through successive cell divisions for regulatory events that determine cell cycle progression or exit in progeny cells. Here we establish that mammalian Runx2 not only controls lineage commitment and cell proliferation by regulating genes transcribed by RNA Pol II, but also acts as a repressor of RNA Pol I mediated rRNA synthesis. Within the condensed mitotic chromosomes we find that Runx2 is retained in large discrete foci at nucleolar organizing regions where rRNA genes reside. These Runx2 chromosomal foci are associated with open chromatin, co-localize with the RNA Pol I transcription factor UBF1, and undergo transition into nucleoli at sites of rRNA synthesis during interphase. Ribosomal RNA transcription and protein synthesis are enhanced by Runx2 deficiency that results from gene ablation or RNA interference, whereas induction of Runx2 specifically and directly represses rDNA promoter activity. Runx2 forms complexes containing the RNA Pol I transcription factors UBF1 and SL1, co-occupies the rRNA gene promoter with these factors in vivo, and affects local chromatin histone modifications at rDNA regulatory regions. Thus Runx2 is a critical mechanistic link between cell fate, proliferation and growth control. Our results suggest that lineage-specific control of ribosomal biogenesis may be a fundamental function of transcription factors that govern cell fate.

Original languageEnglish (US)
Pages (from-to)442-446
Number of pages5
JournalNature
Volume445
Issue number7126
DOIs
StatePublished - Jan 25 2007
Externally publishedYes

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Pol1 Transcription Initiation Complex Proteins
rRNA Genes
RNA Polymerase I
Ribosomal DNA
Chromatin
Cell Growth Processes
Transcription Factors
Histone Code
Cell Proliferation
Ribosomal RNA
RNA Polymerase II
Ribosomal Proteins
Nucleic Acid Regulatory Sequences
Interphase
RNA Interference
Genetic Promoter Regions
Cell Division
Genes
Cell Differentiation
Cell Cycle

ASJC Scopus subject areas

  • General

Cite this

Young, D. W., Hassan, M. Q., Pratap, J., Galindo, M., Zaidi, S. K., Lee, S. H., ... Stein, G. S. (2007). Mitotic occupancy and lineage-specific transcriptional control of rRNA genes by Runx2. Nature, 445(7126), 442-446. https://doi.org/10.1038/nature05473

Mitotic occupancy and lineage-specific transcriptional control of rRNA genes by Runx2. / Young, Daniel W.; Hassan, Mohammad Q.; Pratap, Jitesh; Galindo, Mario; Zaidi, Sayyed K.; Lee, Suk Hee; Yang, Xiaoqing; Xie, Ronglin; Javed, Amjad; Underwood, Jean M.; Furcinitti, Paul; Imbalzano, Anthony N.; Penman, Sheldon; Nickerson, Jeffrey A.; Montecino, Martin A.; Lian, Jane B.; Stein, Janet L.; van Wijnen, Andre J; Stein, Gary S.

In: Nature, Vol. 445, No. 7126, 25.01.2007, p. 442-446.

Research output: Contribution to journalArticle

Young, DW, Hassan, MQ, Pratap, J, Galindo, M, Zaidi, SK, Lee, SH, Yang, X, Xie, R, Javed, A, Underwood, JM, Furcinitti, P, Imbalzano, AN, Penman, S, Nickerson, JA, Montecino, MA, Lian, JB, Stein, JL, van Wijnen, AJ & Stein, GS 2007, 'Mitotic occupancy and lineage-specific transcriptional control of rRNA genes by Runx2', Nature, vol. 445, no. 7126, pp. 442-446. https://doi.org/10.1038/nature05473
Young DW, Hassan MQ, Pratap J, Galindo M, Zaidi SK, Lee SH et al. Mitotic occupancy and lineage-specific transcriptional control of rRNA genes by Runx2. Nature. 2007 Jan 25;445(7126):442-446. https://doi.org/10.1038/nature05473
Young, Daniel W. ; Hassan, Mohammad Q. ; Pratap, Jitesh ; Galindo, Mario ; Zaidi, Sayyed K. ; Lee, Suk Hee ; Yang, Xiaoqing ; Xie, Ronglin ; Javed, Amjad ; Underwood, Jean M. ; Furcinitti, Paul ; Imbalzano, Anthony N. ; Penman, Sheldon ; Nickerson, Jeffrey A. ; Montecino, Martin A. ; Lian, Jane B. ; Stein, Janet L. ; van Wijnen, Andre J ; Stein, Gary S. / Mitotic occupancy and lineage-specific transcriptional control of rRNA genes by Runx2. In: Nature. 2007 ; Vol. 445, No. 7126. pp. 442-446.
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AU - Furcinitti, Paul

AU - Imbalzano, Anthony N.

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