Maintenance of Silent Chromatin through Replication Requires SWI/SNF-like Chromatin Remodeler SMARCAD1

Epigenetic marks such as posttranslational histone modifications specify the functional states of underlying DNA sequences, though how they are maintained after their disruption during DNA replication remains a critical question. We identify the mammalian SWI/SNF-like protein SMARCAD1 as a key factor required for the re-establishment of repressive chromatin. The ATPase activity of SMARCAD1 is necessary for global deacetylation of histones H3/H4. In this way, SMARCAD1 promotes methylation of H3K9, the establishment of heterochromatin, and faithful chromosome segregation. SMARCAD1 associates with transcriptional repressors including KAP1, histone deacetylases HDAC1/2 and the histone methyltransferase G9a/GLP and modulates the interaction of HDAC1 and KAP1 with heterochromatin. SMARCAD1 directly interacts with PCNA, a central component of the replication machinery, and is recruited to sites of DNA replication. Our findings suggest that chromatin remodeling by SMARCAD1 ensures that silenced loci, such as pericentric heterochromatin, are correctly perpetuated. ► SMARCAD1 is required for heterochromatin maintenance and for proper chromosome segregation ► SMARCAD1 regulates histone acetylation and H3K9 methylation during the cell cycle ► SMARCAD1 targets replication sites and directly interacts with PCNA in vivo ► SMARCAD1 interacts with HDAC1 and KAP1 and is required for their binding to heterochromatin