Evolutionarily conserved replication timing profiles predict long-range chromatin interactions and distinguish closely related cell types.

By T. Ryba, I. Hiratani, Junjie Lu, M. Itoh, M. Kulik, Jinfeng Zhang, T. Schulz, A. Robins, S. Dalton, D. Gilbert. Genome Research, 2010

603 citations recorded by the source corpus.

To identify evolutionarily conserved features of replication timing and their relationship to epigenetic properties, we profiled replication timing genome-wide in four human embryonic stem cell (hESC) lines, hESC-derived neural precursor cells (NPCs), lymphoblastoid cells, and two human induced pluripotent stem cell lines (hiPSCs), and compared them with related mouse cell types. Results confirm the conservation of coordinately replicated megabase-sized "replication domains" punctuated by origin-suppressed regions. Differentiation-induced replication timing changes in both species occur in 400- to 800-kb units and are similarly coordinated with transcription changes. A surprising degree of cell-type-specific conservation in replication timing was observed across regions of conserved synteny, despite considerable species variation in the alignment of replication timing to isochore GC/LINE-1 content. Notably, hESC replication timing profiles were significantly more aligned to mouse epiblast-derived stem cells (mEpiSCs) than to mouse ESCs. Comparison with epigenetic marks revealed a signature of chromatin modifications at the boundaries of early replicating domains and a remarkably strong link between replication timing and spatial proximity of chromatin as measured by Hi-C analysis. Thus, early and late initiation of replication occurs in spatially separate nuclear compartments, but rarely within the intervening chromatin. Moreover, cell-type-specific conservation of the replication program implies conserved developmental changes in spatial organization of chromatin. Together, our results reveal evolutionarily conserved aspects of developmentally regulated replication programs in mammals, demonstrate the power of replication profiling to distinguish closely related cell types, and strongly support the hypothesis that replication timing domains are spatially compartmentalized structural and functional units of three-dimensional chromosomal architecture.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6b0087ebc9886d918bd20b7dc902b629824f01a2

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Citations in the corpus

Statistical confidence estimation for Hi-C data reveals regulatory chromatin contacts (2014, background): “In addition, our results suggest an additional level of colocalization among loci that replicate at similar times (Ryba et al., 2010).”
Charting histone modifications and the functional organization of mammalian genomes (2011, background): “Genome-wide profiling of replication timing in mouse and human cells revealed a correlation between replication domains and chromatin structur”
Complex multi-enhancer contacts captured by Genome Architecture Mapping (GAM) (2017, neutral): “As expected, we found that the mean percentage coverage of NPs containing chromosomes 1, 2, 9, 11 and 14 negatively correlates with their radial position, previously measured in Mayer et al. (2005)35.”
A Comparative Encyclopedia of DNA Elements in the Mouse Genome (2014, methodology): “Although conservation of replication timing between mouse and human has been reported 26,27 , the conservation of replicating timing boundaries has not been examined.”
Topologically-associating domains are stable units of replication-timing regulation (2014, positive): “Early and late replication correlate strongly with open and closed chromatin compartments identified by high-resolution chromosome conformation capture (Hi-C), and, to a lesser extent, lamina-associated domains (LADs) 4,5,8,9 .”
Chromatin replication and epigenome maintenance (2012, background): “Moreover, replication timing matches well with recent genome-wide maps of long-range genome interaction”
Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization (2017, neutral): “, 2015)) which replicate late in S-phase (Ryba et al., 2010).”