Leading science, pioneering therapies
CRM Publications

Chromatin decondensation is sufficient to alter nuclear organization in embryonic stem cells.

TitleChromatin decondensation is sufficient to alter nuclear organization in embryonic stem cells.
Publication TypeJournal Article
Year of Publication2014
AuthorsTherizols P, Illingworth R, Courilleau C, Boyle S, Wood AJ, Bickmore WA
Date Published2014 Dec 05
KeywordsAnimals, Cell Differentiation, Cell Line, Cell Nucleus, Chromatin, Chromatin Assembly and Disassembly, DNA Replication, Embryonic Stem Cells, Epigenesis, Genetic, Mice, Nuclear Envelope, Trans-Activators, Transcriptional Activation

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.

Alternate JournalScience
PubMed ID25477464
Grant List102560 / / Wellcome Trust / United Kingdom
MC_PC_U127527202 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom
Publication institute