Dynamics of histone H3.3 deposition in proliferating and senescent cells reveals a DAXX-dependent targeting to PML-NBs important for pericentromeric heterochromatin organization.
Dynamics of histone H3.3 deposition in proliferating and senescent cells reveals a DAXX-dependent targeting to PML-NBs important for pericentromeric heterochromatin organization.
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DOI：
10.4161/cc.26988
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Stucki M
中科院分区：
文献类型：
--
作者：
Corpet A;Olbrich T;Gwerder M;Fink D;Stucki M
癌基因诱导的衰老是一种以广泛的染色质重组为特征的永久性细胞周期阻滞。在这里，我们研究了组蛋白H3变异在人类原代衰老细胞中的特异性靶向和动力学。我们发现新合成的表位标记的H3.3在衰老细胞中结合，但不会在衰老相关的异染色质灶（SAHF）中积累。相反，我们观察到新的H3.3在早幼粒细胞白血病核小体（PML-NBs）中与其特异性组蛋白伴侣共定位，并以daxx依赖的方式靶向增殖细胞和衰老细胞中的PML-NBs。我们进一步表明，DAXX的过表达增强了缺乏转录活性的大PML-NBs中H3.3的靶向性，并促进了HP1的积累，而不依赖于H3K9me3。DAXX或PML耗竭时，中心周围异染色质中H3.3的丢失表明，H3.3靶向PML- nbs与中心周围异染色质组织有关。总之，我们的研究结果强调了非分裂衰老细胞中不依赖复制的染色质组装途径对组蛋白替代的重要性，并建立了PML-NBs作为新H3.3进入染色质的重要调控位点。
Oncogene-induced senescence is a permanent cell cycle arrest characterized by extensive chromatin reorganization. Here, we investigated the specific targeting and dynamics of histone H3 variants in human primary senescent cells. We show that newly synthesized epitope-tagged H3.3 is incorporated in senescent cells but does not accumulate in senescence-associated heterochromatin foci (SAHF). Instead, we observe that new H3.3 colocalizes with its specific histone chaperones within the promyelocytic leukemia nuclear bodies (PML-NBs) and is targeted to PML-NBs in a DAXX-dependent manner both in proliferating and senescent cells. We further show that overexpression of DAXX enhances targeting of H3.3 in large PML-NBs devoid of transcriptional activity and promotes the accumulation of HP1, independently of H3K9me3. Loss of H3.3 from pericentromeric heterochromatin upon DAXX or PML depletion suggests that the targeting of H3.3 to PML-NBs is implicated in pericentromeric heterochromatin organization. Together, our results underline the importance of the replication-independent chromatin assembly pathway for histone replacement in non-dividing senescent cells and establish PML-NBs as important regulatory sites for the incorporation of new H3.3 into chromatin.
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影响因子：
64.8
作者：
Bartkova, Jirina;Rezaei, Nousin;Gorgoulis, Vassilis G.
通讯作者：
Gorgoulis, Vassilis G.
影响因子：
16
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Narita, Masashi
影响因子：
5.3
作者：
Denchi, EL;Attwooll, C;Helin, K
通讯作者：
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影响因子：
7
作者：
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影响因子：
16.8
作者：
Burgess, Rebecca J.;Zhang, Zhiguo
通讯作者：
Zhang, Zhiguo