Proposed model showing that nucleolar silencing is regulated by histone H3K4 demethylation by Jhd2. One unit of the budding yeast rDNA is shown. The triangle and bent arrow indicate a 5S rRNA gene and the transcription start site for a 35S pre-rRNA gene, respectively, which are separated by two NTSs, NTS1 and NTS2. The numbers in colored circles represent methylated lysine residues on histone H3, namely methylated histone H3K4, H3K36 or H3K79. During the G1 to late mitotic phases, the histone H3 methylases Set1, Set2 and Dot1 primarily regulate rDNA recombination and nucleolar silencing in a Sir2-dependent manner; Set1 or Dot1 positively recruits the RENT components Net1 and Sir2 at both the NTS1 and NTS2 regions of the rDNA repeats, whereas Set2 has an opposing effect. During mitosis, however, both rDNA recombination and nucleolar silencing are regulated by the H3K4 demethylase Jhd2 in a Sir2-independent manner.