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Spt6 是着丝粒 CENP-A 的维持因子。

Spt6 is a maintenance factor for centromeric CENP-A.

机构信息

Wellcome Centre for Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, EH9 3BF, UK.

Faculty of Biology, Albert-Ludwigs-Universität Freiburg, 79104, Freiburg, Germany.

出版信息

Nat Commun. 2020 Jun 10;11(1):2919. doi: 10.1038/s41467-020-16695-7.

DOI:10.1038/s41467-020-16695-7
PMID:32522980
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7287101/
Abstract

Replication and transcription of genomic DNA requires partial disassembly of nucleosomes to allow progression of polymerases. This presents both an opportunity to remodel the underlying chromatin and a danger of losing epigenetic information. Centromeric transcription is required for stable incorporation of the centromere-specific histone dCENP-A in M/G1 phase, which depends on the eviction of previously deposited H3/H3.3-placeholder nucleosomes. Here we demonstrate that the histone chaperone and transcription elongation factor Spt6 spatially and temporarily coincides with centromeric transcription and prevents the loss of old CENP-A nucleosomes in both Drosophila and human cells. Spt6 binds directly to dCENP-A and dCENP-A mutants carrying phosphomimetic residues alleviate this association. Retention of phosphomimetic dCENP-A mutants is reduced relative to wildtype, while non-phosphorylatable dCENP-A retention is increased and accumulates at the centromere. We conclude that Spt6 acts as a conserved CENP-A maintenance factor that ensures long-term stability of epigenetic centromere identity during transcription-mediated chromatin remodeling.

摘要

基因组 DNA 的复制和转录需要部分拆开核小体，以允许聚合酶前进。这既提供了重塑基础染色质的机会，也带来了丢失表观遗传信息的风险。着丝粒转录是在 M/G1 期稳定掺入着丝粒特异性组蛋白 dCENP-A 所必需的，这依赖于先前沉积的 H3/H3.3-占位核小体的驱逐。在这里，我们证明了组蛋白伴侣和转录延伸因子 Spt6 在空间和时间上与着丝粒转录一致，并防止在果蝇和人类细胞中丢失旧的 CENP-A 核小体。Spt6 直接结合 dCENP-A，并且携带磷酸模拟残基的 dCENP-A 突变体减轻了这种结合。与野生型相比，磷酸模拟 dCENP-A 突变体的保留减少，而不可磷酸化的 dCENP-A 保留增加，并在着丝粒处积累。我们得出结论，Spt6 作为一种保守的 CENP-A 维持因子，确保了在转录介导的染色质重塑过程中，表观遗传着丝粒身份的长期稳定性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7287101/a789095b2ef6/41467_2020_16695_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7287101/fe0fb8f5bab2/41467_2020_16695_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7287101/aefb2c376c0c/41467_2020_16695_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7287101/c8e64e1bfaea/41467_2020_16695_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7287101/2ad1be1c9d01/41467_2020_16695_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7287101/ea56f8b994bf/41467_2020_16695_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7287101/f163f00abbc5/41467_2020_16695_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7287101/a789095b2ef6/41467_2020_16695_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7287101/fe0fb8f5bab2/41467_2020_16695_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7287101/aefb2c376c0c/41467_2020_16695_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7287101/c8e64e1bfaea/41467_2020_16695_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7287101/2ad1be1c9d01/41467_2020_16695_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7287101/ea56f8b994bf/41467_2020_16695_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7287101/f163f00abbc5/41467_2020_16695_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61f0/7287101/a789095b2ef6/41467_2020_16695_Fig7_HTML.jpg

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