title: Replication timing profile reflects the distinct functional and genomic features of the MHC class II region.
abstract: The timing of DNA replication generally correlates with transcription, gene density and sequence composition. How is the timing affected if a genomic region has a combination of features that individually correlate with either early or late replication? The major histocompatibility complex (MHC) class II region is an AT-rich isochore that would be expected to replicate late, but it also contains coordinately regulated genes that are highly expressed in antigen-presenting cells and are strongly inducible in other cell types. Using cytological and biochemical assays, we find that the entire MHC replicates within the first half of S-phase, and that the class II region replicates slightly later than the adjacent regions irrespective of gene expression. These data suggest that despite AT-richness, an early-to-middle replication time in the class II region is defined by an open chromatin conformation that allows rapid transcriptional activation as a defence against pathogens.
authors.affiliation: Human Cytogenetics Laboratory, Cancer Research, UK London Research Institute, London, UK.
authors.forename: Petros
authors.initials: P
authors.lastname: Takousis
authors.forename: Peter
authors.initials: P
authors.lastname: Johonnett
authors.forename: Jill
authors.initials: J
authors.lastname: Williamson
authors.forename: Peter
authors.initials: P
authors.lastname: Sasieni
authors.forename: Gary
authors.initials: G
authors.lastname: Warnes
authors.forename: Tim
authors.initials: T
authors.lastname: Forshew
authors.forename: Veronique
authors.initials: V
authors.lastname: Azuara
authors.forename: Amanda
authors.initials: A
authors.lastname: Fisher
authors.forename: Pei-Jun
authors.initials: PJ
authors.lastname: Wu
authors.forename: Tania
authors.initials: T
authors.lastname: Jones
authors.forename: Radost
authors.initials: R
authors.lastname: Vatcheva
authors.forename: Stephan
authors.initials: S
authors.lastname: Beck
authors.forename: Denise
authors.initials: D
authors.lastname: Sheer
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D042522:DNA Replication Timing; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma