Angiogenin undergoes nuclear translocation in endothelial and smooth muscle 
cells where it accumulates in the nucleolus and binds to DNA. Nuclear 
translocation of angiogenin is necessary for its biological activity and is 
mediated by an endocytotic pathway that is independent of the microtubule system 
and lysosomal processing. Because the nucleolus is a subnuclear organelle 
containing clusters of transcriptionally active ribosomal RNA genes, we studied 
the binding of angiogenin to the intergenic spacer of the ribosomal RNA gene 
where many of the transcription regulatory elements are located. Here we report 
that angiogenin binds to CT repeats that are abundant in the nontranscribed 
region of the ribosomal RNA gene. An angiogenin-binding DNA sequence 
(CTCTCTCTCTCTCTCTCCCTC) has been identified and designated angiogenin-binding 
element (ABE). ABE binds angiogenin specifically and exhibits 
angiogenin-dependent promoter activity in a luciferase reporter system. CT 
repeats, or inverted GA box, which are abundantly distributed in the eukaryotic 
genome and are often located in the 5'-flanking region, have been implicated in 
regulating gene expression. We have previously shown that angiogenin stimulates 
rRNA synthesis. The present results suggest that the nuclear function of 
angiogenin may not only be related to rRNA production but also play a role in 
regulating expression of genes containing CT repeats.