RESEARCH HIGHLIGHTS

Nature Reviews Molecular Biology | AOP, published online 5 January 2015; doi:10.1038/nrm3938

of target loci without activating transcription. Interestingly, decondensation at Ptn, Sox6 and Nrp1 (which was similar to that observed during ES cell differentiation) was sufficient to induce the relocation of each locus BRAND X PICTURES towards the centre of nuclei, indicating that nuclear reorganization is driven by chromatin remodelling. CHROMATIN As Ptn, Sox6 and Nrp1 activation during ES cell to NPC differentiation is normally accompanied with a shift of replication timing from late Drivers of nuclear organization to early S phase, the authors analysed how TALE transfection affects The organization of eukaryotic nuclei is to neural precursor cells (NPCs). To understand the replication timing at these loci. TALE fused to conserved: , poorly transcribed relationship between nuclear reorganization and VP64 advanced replication timing, whereas and late-replicating chromatin domains are transcription, the three were ectopically TALE fused to the acidic domain had no effect, usually located at the nuclear periphery, whereas expressed using synthetic transcription factors suggesting that the switch to early replication actively transcribed loci and early-replicating containing TALE (transcription-activator-like requires transcriptional activation. domains have more central locations. However, effector) DNA-binding domains specific for each Thus, this study indicates that nuclear it remains unclear whether changes in position fused to a transcriptional activator reorganization during differentiation is a of chromatin relative to the nuclear envelope domain (VP64). Transfection of these transcription consequence of chromatin regulation and are a cause or a consequence of regulation. factors in ES cells activated Ptn, Sox6 and Nrp1 that changes in replication timing are a direct Data from Bickmore and colleagues now suggest and induced the relocalization of the targeted loci consequence of transcription. Further studies that chromatin remodelling is sufficient to induce from the periphery to the centre of ES cell nuclei. should provide insights into the chromatin nuclear reorganization. These observations suggest that forced gene modifications that are associated with The authors studied three genes (pleiotrophin expression induces relocalization to the nucleus these changes. (Ptn), Sox6 and neuropilin 1 (Nrp1)) that are centre independently of differentiation. Kim Baumann transcriptionally upregulated, and that move from Next, the authors replaced the transactivation ORIGINAL RESEARCH PAPER Therizols, P. et al. Chromatin the nuclear periphery to the centre, during the domain of the TALE transcription factor with decondensation is sufficient to alter nuclear organization in differentiation of mouse embryonic stem (ES) cells an acidic peptide that decondenses chromatin embryonic stem cells. Science 346, 1238–1242 (2014)

NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUME 16 | FEBRUARY 2015

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