CRAMPED (CRM), conserved from plants to animals, was previously characterized genetically as a repressive factor involved in the formation of facultative and constitutive heterochromatin (Polycomb silencing, position effect variegation). We show that crm is dynamically regulated during replication and identify the Histone gene cluster (His-C) as a major CRM target. Surprisingly, CRM is specifically required for the expression of the Histone H1 gene, like the promoter-bound transcription factor TRF2. Consistently with this, CRM genetically interacts and co-immunoprecipitates with TRF2. However, the Polycomb phenotypes observed in crm mutants are not observed in TRF2 hypomorphic mutants, suggesting that they correspond to independent roles of CRM. CRM is thus a highly pleiotropic factor involved in both activation and repression.