Replication timing profile reflects the distinct functional and genomic features of the MHC class II region.
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.
Takousis
Petros
P
Human Cytogenetics Laboratory, Cancer Research, UK London Research Institute, London, UK.
Johonnett
Peter
P
Williamson
Jill
J
Sasieni
Peter
P
Warnes
Gary
G
Forshew
Tim
T
Azuara
Veronique
V
Fisher
Amanda
A
Wu
Pei-Jun
PJ
Jones
Tania
T
Vatcheva
Radost
R
Beck
Stephan
S
Sheer
Denise
D
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
D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma