Figure 3. Spp1 swaps function. (A) 1- At activated genes, the Paf1 complex mediates the association of Bre1/Rad6 and Set1C to RNAP II39 allowing the transient ubiquitylation of H2BK123 and H3K4 trimethylation of the first nucleosomes of transcribed genes (see 11 for a review). Two and 3- Along the coding regions of the genes, di- and then monomethylation of H3K4 correlate with a gradual reduction of the binding of Set1C.22 We envisage that unknown post-translational modifications facilitate the specific release of Spp1 from the Set1C (B and C) During meiotic differentiation, the interaction of Spp1 with H3K4me3 and the chromatin axis-associated protein Mer2 offers an explanation of the mechanism that select the potential meiotic DSB sites that are brought to the chromosome axis for further cleavage by Spo11.37,38 Our results indicate that H3K4me3 is required for the function of Spp1 probably through its recognition by the Spp1 PHD-domain, a requirement that can be bypassed by tethering Spp1.37 NDR = Nucleosome depleted regions, Mer2 ID = Mer2 interacting domain. Mer2-p = Phosphorylated Mer2.