RGD Reference Report - Mitotic occupancy and lineage-specific transcriptional control of rRNA genes by Runx2. - Rat Genome Database

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

Authors: 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 
Citation: Young DW, etal., Nature. 2007 Jan 25;445(7126):442-6.
RGD ID: 13432326
Pubmed: PMID:17251981   (View Abstract at PubMed)
DOI: DOI:10.1038/nature05473   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Runx2Ratprotein binding enablesIPIUniProtKB:P25977PMID:17251981IntAct 
UbtfRatprotein binding enablesIPIUniProtKB:Q9Z2J9PMID:17251981IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Runx2  (RUNX family transcription factor 2)
Ubtf  (upstream binding transcription factor)


Additional Information