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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.

Original publication

DOI

10.1016/j.molcel.2011.02.036

Type

Journal article

Journal

Mol Cell

Publication Date

06/05/2011

Volume

42

Pages

285 - 296

Keywords

Acetylation, Adenosine Triphosphatases, Animals, Blotting, Western, Cell Line, Cells, Cultured, Chromatin, DNA Helicases, DNA Replication, Gene Expression Regulation, HEK293 Cells, HeLa Cells, Heterochromatin, Histone Deacetylase 1, Histone-Lysine N-Methyltransferase, Histones, Humans, Methylation, Mice, NIH 3T3 Cells, Proliferating Cell Nuclear Antigen, Protein Binding, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, S Phase