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.

Alterations of chromatin structure play an important role in gene regulation. One way of doing so involves ATP-dependent chromatin remodelling enzymes that act as molecular machines coupling ATP-hydrolysis to structural changes of the nucleosome. Several recent studies shed important insights into the mechanism of these factors and indicate that they couple DNA translocation within the nucleosome to DNA loop propagation through the nucleosome. This reaction causes the movement of a nucleosome with respect to a given DNA sequence and also drives its disassembly. It is becoming clear that the biology of these factors is very complex considering the plethora of known ATP-dependent nucleosome remodelling factors and their many, in part overlapping functions and varied ways of regulation and targeting. Finally, nucleosome remodelling may only be one aspect of the function of these enzymes, because they may impart or regulate higher order levels of chromatin organization. The importance of these enzymes for normal growth and development is illustrated by disorders and neoplasias linked to mutations of those factors or their misregulation. Given that these enzymes have such profound roles in gene expression and cell proliferation, they may constitute important drug targets for clinical applications in the future

Alterations of chromatin structure play an important role in gene regulation. One way of doing so involves ATP-dependent chromatin remodelling enzymes that act as molecular machines coupling ATP-hydrolysis to structural changes of the nucleosome. Several recent studies shed important insights into the mechanism of these factors and indicate that they couple DNA translocation within the nucleosome to DNA loop propagation through the nucleosome. This reaction causes the movement of a nucleosome with respect to a given DNA sequence and also drives its disassembly. It is becoming clear that the biology of these factors is very complex considering the plethora of known ATP-dependent nucleosome remodelling factors and their many, in part overlapping functions and varied ways of regulation and targeting. Finally, nucleosome remodelling may only be one aspect of the function of these enzymes, because they may impart or regulate higher order levels of chromatin organization. The importance of these enzymes for normal growth and development is illustrated by disorders and neoplasias linked to mutations of those factors or their misregulation. Given that these enzymes have such profound roles in gene expression and cell proliferation, they may constitute important drug targets for clinical applications in the future

Alterations of chromatin structure play an important role in gene regulation. One way of doing so involves ATP-dependent chromatin remodelling enzymes that act as molecular machines coupling ATP-hydrolysis to structural changes of the nucleosome. Several recent studies shed important insights into the mechanism of these factors and indicate that they couple DNA translocation within the nucleosome to DNA loop propagation through the nucleosome. This reaction causes the movement of a nucleosome with respect to a given DNA sequence and also drives its disassembly. It is becoming clear that the biology of these factors is very complex considering the plethora of known ATP-dependent nucleosome remodelling factors and their many, in part overlapping functions and varied ways of regulation and targeting. Finally, nucleosome remodelling may only be one aspect of the function of these enzymes, because they may impart or regulate higher order levels of chromatin organization. The importance of these enzymes for normal growth and development is illustrated by disorders and neoplasias linked to mutations of those factors or their misregulation. Given that these enzymes have such profound roles in gene expression and cell proliferation, they may constitute important drug targets for clinical applications in the future