The SENP7 SUMO-Protease Presents a Module of Two HP1 Interaction Motifs that Locks HP1 Protein at Pericentric Heterochromatin

HP1 enrichment at pericentric heterochromatin is essential for proper chromosome segregation. While H3K9me3 is thought to be a major contributor to HP1 enrichment at pericentric domains, in mouse cells, the SUMO-protease SENP7 is required in addition to H3K9me3. How this is achieved remains elusive. Here, wefind that loss of SENP7 leads to an increased time spent in mitosis. Furthermore, we reveal that a short module comprising two consecutive HP1 interaction motifs on SENP7 is the determinant for HP1 enrichment and acts by restricting HP1 mobility at pericentric domains. We propose a mechanism for maintenance of HP1 enrichment in which this module functions on top of H3K9me3 to lock contiguous HP1 molecules already docked on H3K9me3-modified nucleosomes. H3K9me3 would thus promote HP1 enrichment only if a locking system is in place. This mechanism may apply to other nuclear domains to contribute to the control of genome plasticity and integrity.