title: Chromatin remodeling by WSTF-ISWI at the replication site: opening a window of opportunity for epigenetic inheritance?
abstract: During DNA replication, chromatin states have to be accurately transmitted from the parental to the daughter strands for faithful epigenetic inheritance. Chromatin remodelling factors at the replication site are thought to be involved in this process. Recent work adds ATP-dependent nucleosome remodelling factors to this category of enzymes. The WICH complex, consisting of the ISWI-type ATPase SNF2H and the Williams Syndrome Transcription Factor (WSTF), binds to replication foci using PCNA, a key factor in DNA- and chromatin replication and DNA repair, as an interaction platform. Depletion of WSTF results in decreased chromatin accessibility, which is evident already in newly replicated DNA. This leads to heterochromatin formation on a global scale and a decrease in overall transcriptional activity. Here, we propose that WICH, by keeping nucleosomes mobile, provides access to the newly replicated DNA and may thereby create a window of opportunity after DNA replication for rebinding of factors that maintain the epigenetic state, and thus prevents aberrant heterochromatin formation. Our model may provide an explanation for the long-standing observation of a delay in chromatin "maturation" on newly replicated DNA, by connecting this delay with the action of PCNA-bound WSTF-ISWI, and highlights chromatin remodeling shortly after DNA replication as a critical point for regulation.
authors.affiliation: Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, UK.
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Poot
authors.forename: Ludmila
authors.initials: L
authors.lastname: Bozhenok
authors.forename: Debbie L C
authors.initials: DL
authors.lastname: van den Berg
authors.forename: Nicola
authors.initials: N
authors.lastname: Hawkes
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Varga-Weisz
mesh_terms: D000251:Adenosine Triphosphatases / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle; D002843:Chromatin / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D004261:DNA Replication; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006570:Heterochromatin / Q000737:chemistry; D006801:Humans; D008954:Models, Biological; D009707:Nucleosomes / Q000737:chemistry; D011485:Protein Binding; D014157:Transcription Factors / Q000502:physiology*; D000092468:Bromodomain Containing Proteins
chemical_list: D000251:Adenosine Triphosphatases; D002843:Chromatin; D004247:DNA; D006570:Heterochromatin; D009707:Nucleosomes; D014157:Transcription Factors; C116750:BAZ1B protein, human; D000092468:Bromodomain Containing Proteins; C086468:ISWI protein