Structural organization of human replication timing domains

Abstract

a b s t r a c tRecent analysis of genome-wide epigenetic modification data, mean replication timing (MRT) profiles and chromosome conformation data in mammals have provided increasing evidence that flexibility in replication origin usage is regulated locally by the epigenetic landscape and over larger genomic distances by the 3D chromatin architecture. Here, we review the recent results establishing some link between replication domains and chromatin structural domains in pluripotent and various differentiated cell types in human. We reconcile the originally proposed dichotomic picture of early and late constant timing regions that replicate by multiple rather synchronous origins in separated nuclear compartments of open and closed chromatins, with the U-shaped MRT domains bordered by ''master'' replication origins specified by a localized ($200-300 kb) zone of open and transcriptionally active chromatin from which a replication wave likely initiates and propagates toward the domain center via a cascade of origin firing. We discuss the relationships between these MRT domains, topologically associated domains and lamina-associated domains. This review sheds a new light on the epigenetically regulated global chromatin reorganization that underlies the loss of pluripotency and the determination of differentiation properties.

Replicating Large Genomes: Divide and Conquer

“…Regulation of DNA replication in eukaryotes has been the topic of several outstanding recent reviews (Boulos et al, 2015; Deegan and Diffley, 2016; Fragkos et al, 2015; Hyrien, 2015; Urban et al, 2015). Here we briefly highlight the mechanisms that ensure one complete round of DNA replication.…”

Genome-wide analysis of replication timing by next-generation sequencing with E/L Repli-seq

“…Typical downstream analyses include comparisons of RT profiles to other genomics data such as epigenetic marks, chromatin conformation or lamina-association 13,26,27 , as well as examining differences between datasets to find cell-type or disease-specific RT patterns or the effects of genetic manipulations. RT is highly cell type specific, with 50% of the genome changing RT across many mammalian cell types 2–6,8 .…”

Genomic Analysis of the DNA Replication Timing Program during Mitotic S Phase in Maize (Zea mays) Root Tips

“…Some have hypothesized that these TTRs consist of unidirectional replication forks spreading from origins active earlier in S phase (Hiratani et al, 2008;Ryba et al, 2010), while others have argued that such regions contain origins activated in a "cascading" or "domino" pattern by earlier firing origins nearby (Guilbaud et al, 2011). There has been much less debate over the patterns of activation of origins firing within the constant timing region domains, as these are thought to activate roughly synchronously in clusters (Jackson and Pombo, 1998;Blow et al, 2011;Boulos et al, 2015;Klein and Gilbert, 2016).…”