Sign up for Table of Contents Alerts.

Email this page

Print this page

Report

Replication Timing Profile Reflects the Distinct Functional and Genomic Features of the MHC Class II Region

Petros Takousis, Peter Johonnett, Jill Williamson, Peter Sasieni, Gary Warnes, Tim Forshew, Veronique Azuara, Amanda Fisher, Pei-Jun Wu, Tania Jones, Radost Vatcheva, Stephan Beck and Denise Sheer

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.

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

Petros Takousis

Cancer Research UK London Research Institute; London UK

Peter Johonnett

Cancer Research UK London Research Institute; London UK

Jill Williamson

Cancer Research UK London Research Institute; London UK

Peter Sasieni

Wolfson Institute of Preventive Medicine; London UK

Gary Warnes

Queen Mary's School of Medicine and Dentistry; London UK

Tim Forshew

Queen Mary's School of Medicine and Dentistry; London UK

Veronique Azuara

Imperial College School of Medicine; London UK

Amanda Fisher

Imperial College School of Medicine; London UK

Pei-Jun Wu

Cancer Research UK London Research Institute; London UK

Tania Jones

Cancer Research UK London Research Institute; London UK

Radost Vatcheva

Cancer Research UK London Research Institute; London UK

Stephan Beck

Wellcome Trust Sanger Institute; Cambridge UK

Denise Sheer

Queen Mary's School of Medicine and Dentistry; London UK

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.