Interaction of nucleolin with ribosomal RNA genes and its role in RNA polymerase I transcription

Nucleolin is a multi-functional nucleolar protein that is required for ribosomal RNA gene (rRNA) tran-scription in vivo, but the mechanism by which nucleolin modulates RNA polymerase I (RNAPI) tran-scription is not well understood. Nucleolin depletion results in an increase in the heterochromatin mark H3K9me2 and a decrease in H4K12Ac and H3K4me3 euchromatin histone marks in rRNA genes. ChIP-seq experiments identified an enrichment of nucleolin in the ribosomal DNA (rDNA) coding and promoter region. Nucleolin is preferentially associ-ated with unmethylated rRNA genes and its deple-tion leads to the accumulation of RNAPI at the beginning of the transcription unit and a decrease in UBF along the coding and promoter regions. Nucleolin is able to affect the binding of transcrip-tion termination factor-1 on the promoter-proximal terminator T0, thus inhibiting the recruitment of TIP5 and HDAC1 and the establishment of a repressive heterochromatin state. These results reveal the importance of nucleolin for the maintenance of the euchromatin state and transcription elongation of rDNA