DAXX-dependent supply of soluble (H3.3-H4) dimers to PML bodies pending deposition into chromatin.

DAXX-dependent supply of soluble (H3.3-H4) dimers to PML bodies pending deposition into chromatin.
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DOI:
10.1101/gr.142703.112
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发表时间:
2013-03
期刊:
影响因子:
7
通讯作者:
Collas P
Collas P
中科院分区:
生物学1区
文献类型:
--
作者:
Delbarre E;Ivanauskiene K;Küntziger T;Collas P

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组蛋白变异体H3.3的不依赖复制的染色质沉积是由几个伴侣介导的。我们报道了通过PML小体将新合成的表位标记的H3.3多步靶向染色质。H3.3以依赖DAXX的方式被招募到PML机构,这一过程由ASF1A促进。用PML浓缩ATRX需要Daxx,但不需要ASF1A或Hira。尽管如此,伴侣与H3.3在PML小体上共定位,并在一个或多个与PML的复合体中被发现。DAXX和PML都是防止H3.3可溶的、未结合的池积累所必需的。针对PML的H3.3靶向被H3.3的(H3.3-H4)2四聚突变体增强,这表明H3.3作为(H3.3-H4)二聚体而不是四聚体募集到PML。我们的数据支持DAXX介导的(H3.3-H4)二聚体到PML小体的募集模型,这可能是H3.3通过不同的伴侣沉积到染色质的分诊中心。
Replication-independent chromatin deposition of histone variant H3.3 is mediated by several chaperones. We report a multistep targeting of newly synthesized epitope-tagged H3.3 to chromatin via PML bodies. H3.3 is recruited to PML bodies in a DAXX-dependent manner, a process facilitated by ASF1A. DAXX is required for enrichment of ATRX, but not ASF1A or HIRA, with PML. Nonetheless, the chaperones colocalize with H3.3 at PML bodies and are found in one or more complexes with PML. Both DAXX and PML are necessary to prevent accumulation of a soluble, nonincorporated pool of H3.3. H3.3 targeting to PML is enhanced with an (H3.3–H4)2 tetramerization mutant of H3.3, suggesting H3.3 recruitment to PML as an (H3.3–H4) dimer rather than as a tetramer. Our data support a model of DAXX-mediated recruitment of (H3.3–H4) dimers to PML bodies, which may function as triage centers for H3.3 deposition into chromatin by distinct chaperones.
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