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

Chromatin decondensation is sufficient to alter nuclear organization in embryonic stem cells.
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DOI:
10.1126/science.1259587
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发表时间:
2014-12-05
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Bickmore WA
Bickmore WA
中科院分区:
其他
文献类型:
--
作者:
Therizols P;Illingworth RS;Courilleau C;Boyle S;Wood AJ;Bickmore WA

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在分化过程中,成千上万的基因被重新定位,朝向或远离核膜。这些运动与转录和复制时间的变化相关。在这里,使用合成转录因子(TALE-TF),我们表明,内源性基因的转录激活病毒的反式激活因子是足以诱导基因重新定位向核内部。然而,基因的重新定位也是由一种酸性肽的募集诱导的,这种酸性肽使染色质去致密化而不影响转录,这表明核重组是由染色质重塑而不是转录驱动的。我们确定了一个表观遗传记忆的基因激活,保持中央核定位通过有丝分裂,即使在TALE TF丢失。最后,我们证明,转录激活,但不是染色质去凝聚,是足以改变复制时间。
During differentiation thousands of genes are repositioned toward or away from the nuclear envelope. These movements correlate with changes in transcription and replication timing. Here, using synthetic transcription factors (TALE-TFs) we show that transcriptional activation of endogenous genes by a viral trans-activator is sufficient to induce gene repositioning toward the nuclear interior. However, gene relocation is 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 identify an epigenetic memory of gene activation, which maintains central nuclear positioning through mitosis even after the TALE-TF is lost. Finally, we demonstrate that transcription activation, but not chromatin decondensation, is sufficient to change replication timing.
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