title: Maintenance of silent chromatin through replication requires SWI/SNF-like chromatin remodeler SMARCAD1.
abstract: 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.
authors.affiliation: Nuclear Dynamics and Function, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Samuel P
authors.initials: SP
authors.lastname: Rowbotham
authors.forename: Leila
authors.initials: L
authors.lastname: Barki
authors.forename: Ana
authors.initials: A
authors.lastname: Neves-Costa
authors.forename: Fatima
authors.initials: F
authors.lastname: Santos
authors.forename: Wendy
authors.initials: W
authors.lastname: Dean
authors.forename: Nicola
authors.initials: N
authors.lastname: Hawkes
authors.forename: Parul
authors.initials: P
authors.lastname: Choudhary
authors.forename: W Ryan
authors.initials: WR
authors.lastname: Will
authors.forename: Judith
authors.initials: J
authors.lastname: Webster
authors.forename: David
authors.initials: D
authors.lastname: Oxley
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Green
authors.forename: Patrick
authors.initials: P
authors.lastname: Varga-Weisz
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Mermoud
mesh_terms: D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D056284:Histone Deacetylase 1 / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D051379:Mice; D041681:NIH 3T3 Cells; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase
chemical_list: D002843:Chromatin; D006570:Heterochromatin; D006657:Histones; D018809:Proliferating Cell Nuclear Antigen; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C412482:SMARCAL1 protein, human; D056284:Histone Deacetylase 1; D000251:Adenosine Triphosphatases; D004265:DNA Helicases