Angiogenin (ANG) undergoes nuclear translocation and promotes ribosomal RNA 
(rRNA) transcription thereby enhancing cell growth and proliferation. However, 
the mode of action of ANG in stimulating rRNA transcription is unclear. Here, we 
show that ANG enhances the formation of RNA polymerase I (Pol I) pre-initiation 
complex at the ribosomal DNA (rDNA) promoter. ANG binds at the upstream control 
element (UCE) of the promoter and enhances promoter occupancy of RNA Pol I as 
well as the selectivity factor SL1 components TAFI 48 and TAFI 110. We also show 
that ANG increases the number of actively transcribing rDNA by epigenetic 
activation through promoter methylation and histone modification. ANG binds to 
histone H3, inhibits H3K9 methylation, and activates H3K4 methylation as well as 
H4 acetylation at the rDNA promoter. These data suggest that one of the 
mechanisms by which ANG stimulates rRNA transcription is through an epigenetic 
activation of rDNA promoter.