Structural organization of human replication timing domains.
Recent 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.
Université de Lyon, F-69000 Lyon, France; Laboratoire de Physique, CNRS UMR5672, Ecole Normale Supérieure de Lyon, F-69007 Lyon, France.
Rasha E
RE
Boulos
Université de Lyon, F-69000 Lyon, France; Laboratoire de Physique, CNRS UMR5672, Ecole Normale Supérieure de Lyon, F-69007 Lyon, France.
Guénola
G
Drillon
Université de Lyon, F-69000 Lyon, France; Laboratoire de Physique, CNRS UMR5672, Ecole Normale Supérieure de Lyon, F-69007 Lyon, France.
Françoise
F
Argoul
Université de Lyon, F-69000 Lyon, France; Laboratoire de Physique, CNRS UMR5672, Ecole Normale Supérieure de Lyon, F-69007 Lyon, France.
Alain
A
Arneodo
Université de Lyon, F-69000 Lyon, France; Laboratoire de Physique, CNRS UMR5672, Ecole Normale Supérieure de Lyon, F-69007 Lyon, France. Electronic address: benjamin.audit@ens-lyon.fr.
Benjamin
B
Audit
D000818:Animals; D002467:Cell Nucleus / Q000502:physiology / Q000648:ultrastructure; D002843:Chromatin / Q000502:physiology / Q000648:ultrastructure; D042002:Chromatin Assembly and Disassembly; D004261:DNA Replication; D044127:Epigenesis, Genetic; D006801:Humans; D009690:Nucleic Acid Conformation; D012045:Regulatory Sequences, Nucleic Acid
D002843:Chromatin
Chromatin conformation; Chromatin states; Equilibrium and fractal globule models; Lamina-associated domains; Replication timing domains; Topologically associated domains