The Arabidopsis histone deacetylase HDA6 is required to silence transgenes, 
transposons, and ribosomal RNA (rRNA) genes subjected to nucleolar dominance in 
genetic hybrids. In nonhybrid Arabidopsis thaliana, we show that a class of 45S 
rRNA gene variants that is normally inactivated during development fails to be 
silenced in hda6 mutants. In these mutants, symmetric cytosine methylation at CG 
and CHG motifs is reduced, and spurious RNA polymerase II (Pol II) transcription 
occurs throughout the intergenic spacers. The resulting sense and antisense 
spacer transcripts facilitate a massive overproduction of siRNAs that, in turn, 
direct de novo cytosine methylation of corresponding gene sequences. However, 
the resulting de novo DNA methylation fails to suppress Pol I or Pol II 
transcription in the absence of HDA6 activity; instead, euchromatic histone 
modifications typical of active genes accumulate. Collectively, the data reveal 
a futile cycle of unregulated transcription, siRNA production, and 
siRNA-directed DNA methylation in the absence of HDA6-mediated histone 
deacetylation. We propose that spurious Pol II transcription throughout the 
intergenic spacers in hda6 mutants, combined with losses of histone deacetylase 
activity and/or maintenance DNA methylation, eliminates repressive chromatin 
modifications needed for developmental rRNA gene dosage control.