title: Chromatin decondensation is sufficient to alter nuclear organization in embryonic stem cells.
abstract: During differentiation, thousands of genes are repositioned toward or away from the nuclear envelope. These movements correlate with changes in transcription and replication timing. Using synthetic (TALE) transcription factors, we found that transcriptional activation of endogenous genes by a viral trans-activator is sufficient to induce gene repositioning toward the nuclear interior in embryonic stem cells. However, gene relocation was also induced by recruitment of an acidic peptide that decondenses chromatin without affecting transcription, indicating that nuclear reorganization is driven by chromatin remodeling rather than transcription. We identified an epigenetic inheritance of chromatin decondensation that maintained central nuclear positioning through mitosis even after the TALE transcription factor was lost. Our results also demonstrate that transcriptional activation, but not chromatin decondensation, is sufficient to change replication timing.
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Pierre
authors.initials: P
authors.lastname: Therizols
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Illingworth
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Celine
authors.initials: C
authors.lastname: Courilleau
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Shelagh
authors.initials: S
authors.lastname: Boyle
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wood
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK. wendy.bickmore@igmm.ed.ac.uk.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Bickmore
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004261:DNA Replication; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D044127:Epigenesis, Genetic; D051379:Mice; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D015534:Trans-Activators