期刊
SCIENCE
卷 346, 期 6214, 页码 1238-1242出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1259587
关键词
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资金
- Marie Curie Intra European Fellowship
- Wellcome Trust
- UK Medical Research Council
- European Research Council [249956]
- European Research Council (ERC) [249956] Funding Source: European Research Council (ERC)
- Medical Research Council [MC_PC_U127527202] Funding Source: researchfish
- MRC [MC_PC_U127527202] Funding Source: UKRI
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.
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