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

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Science  05 Dec 2014:
Vol. 346, Issue 6214, pp. 1238-1242
DOI: 10.1126/science.1259587

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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.

Unpacking for travel to the nuclear interior

The position of a gene within the cell nucleus is correlated with its activity. Those near the nuclear periphery are generally repressed, whereas those in the center are (or will be) active. It is not clear whether this relocalization is a cause or a consequence of gene regulation. Therizols et al. found that transcriptional activation or simply chromatin decondensation both drove the relocation of genes to the interior of the nucleus. The nuclear position was maintained in daughter cells, suggesting that the cell has an epigenetic memory of the gene's position within the nucleus.

Science, this issue p. 1238

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