Rapid Irreversible Transcriptional Reprogramming in Human Stem Cells Accompanied by Discordance between Replication Timing and Chromatin Compartment
| Autor: | Daniel A. Bartlett, Korey A. Wilson, Xiaowen Lyu, Rachel Patton McCord, Peiyao A. Zhao, David M. Gilbert, Zhaohui S. Qin, Allan J. Robins, Vishnu Dileep, Ben Li, Thomas C. Schulz, Victor G. Corces, Axel Poulet, Stephen Dalton, Claire Marchal, Michael Kulik, Juan Carlos Rivera-Mulia, Job Dekker |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
chromatin 3D organization Transcription Genetic DNA Replication Timing Cellular differentiation lineage commitment replication timing Biology Models Biological Biochemistry Article Chromosome conformation capture 03 medical and health sciences 0302 clinical medicine Genetics Humans Cell Lineage Epigenetics chromatin 3D architecture lcsh:QH301-705.5 Embryonic Stem Cells chromatin structure lcsh:R5-920 Replication timing Gene Expression Profiling Stem Cells Cell Cycle DNA replication Cell Differentiation differentiation Cell Biology Cell cycle Cellular Reprogramming Chromatin Cell biology 030104 developmental biology lcsh:Biology (General) gene expression lcsh:Medicine (General) Reprogramming 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Stem Cell Reports Stem Cell Reports, Vol 13, Iss 1, Pp 193-206 (2019) |
| ISSN: | 2213-6711 |
| Popis: | Summary The temporal order of DNA replication is regulated during development and is highly correlated with gene expression, histone modifications and 3D genome architecture. We tracked changes in replication timing, gene expression, and chromatin conformation capture (Hi-C) A/B compartments over the first two cell cycles during differentiation of human embryonic stem cells to definitive endoderm. Remarkably, transcriptional programs were irreversibly reprogrammed within the first cell cycle and were largely but not universally coordinated with replication timing changes. Moreover, changes in A/B compartment and several histone modifications that normally correlate strongly with replication timing showed weak correlation during the early cell cycles of differentiation but showed increased alignment in later differentiation stages and in terminally differentiated cell lines. Thus, epigenetic cell fate transitions during early differentiation can occur despite dynamic and discordant changes in otherwise highly correlated genomic properties. Graphical Abstract Highlights • Stable transcriptional reprogramming toward endoderm within one cell cycle • Replication timing can change in the first S phase of a cell fate change • Early discordance between Replication timing and Hi-C compartments • Alignment of replication timing to compartments increases in later cell cycles The temporal order of DNA replication is regulated during development, and is highly correlated with gene expression, chromatin structure, and 3D-genome architecture. Gilbert and colleagues find that stable transcriptional changes of human embryonic stem cells to endoderm can occur within a single cell cycle, accompanied by discordance in replication timing and chromatin compartment that align in later differentiation stages. |
| Databáze: | OpenAIRE |
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