Suppr超能文献

脊椎动物动粒的超分辨率图谱。

A super-resolution map of the vertebrate kinetochore.

机构信息

Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, UK.

出版信息

Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10484-9. doi: 10.1073/pnas.1002325107. Epub 2010 May 18.

Abstract

A longstanding question in centromere biology has been the organization of CENP-A-containing chromatin and its implications for kinetochore assembly. Here, we have combined genetic manipulations with deconvolution and super-resolution fluorescence microscopy for a detailed structural analysis of chicken kinetochores. Using fluorescence microscopy with subdiffraction spatial resolution and single molecule sensitivity to map protein localization in kinetochore chromatin unfolded by exposure to a low salt buffer, we observed robust amounts of H3K9me3, but only low levels of H3K4me2, between CENP-A subdomains in unfolded interphase prekinetochores. Constitutive centromere-associated network proteins CENP-C and CENP-H localize within CENP-A-rich subdomains (presumably on H3-containing nucleosomes) whereas CENP-T localizes in interspersed H3-rich blocks. Although interphase prekinetochores are relatively more resistant to unfolding than sur-rounding pericentromeric heterochromatin, mitotic kinetochores are significantly more stable, reflecting mitotic kinetochore maturation. Loss of CENP-H, CENP-N, or CENP-W had little or no effect on the unfolding of mitotic kinetochores. However, loss of CENP-C caused mitotic kinetochores to unfold to the same extent as their interphase counterparts. Based on our results we propose a new model for inner centromeric chromatin architecture in which chromatin is folded as a layered boustrophedon, with planar sinusoids containing interspersed CENP-A-rich and H3-rich subdomains oriented toward the outer kinetochore. In mitosis, a CENP-C-dependent mechanism crosslinks CENP-A blocks of different layers together, conferring extra stability to the kinetochore.

摘要

中心体生物学中的一个长期问题是含有 CENP-A 的染色质的组织及其对动粒组装的影响。在这里,我们结合遗传操作与去卷积和超分辨率荧光显微镜,对鸡动粒进行了详细的结构分析。利用具有亚衍射空间分辨率和单分子灵敏度的荧光显微镜,在暴露于低盐缓冲液后对动粒染色质进行解折叠,我们观察到在解折叠的间期前期动粒中,H3K9me3 大量存在,但在 CENP-A 亚域之间存在的 H3K4me2 水平较低。组成性着丝粒相关网络蛋白 CENP-C 和 CENP-H 定位于富含 CENP-A 的亚域(推测位于含有 H3 的核小体上),而 CENP-T 定位于散布的富含 H3 的块中。尽管间期前期动粒相对于周围着丝粒异染色质较不易解折叠,但有丝分裂动粒更稳定,反映出有丝分裂动粒的成熟。缺失 CENP-H、CENP-N 或 CENP-W 对有丝分裂动粒的解折叠几乎没有影响。然而,缺失 CENP-C 会导致有丝分裂动粒解折叠的程度与间期动粒相同。基于我们的结果,我们提出了一个新的内着丝粒染色质结构模型,其中染色质作为层状的正反交错结构折叠,含有散布的富含 CENP-A 和富含 H3 的亚域的平面正弦波朝向动粒的外部。在有丝分裂过程中,一种依赖于 CENP-C 的机制将不同层的 CENP-A 块交联在一起,赋予动粒额外的稳定性。

相似文献

1
A super-resolution map of the vertebrate kinetochore.
Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10484-9. doi: 10.1073/pnas.1002325107. Epub 2010 May 18.
2
Stepwise unfolding supports a subunit model for vertebrate kinetochores.
Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3133-3138. doi: 10.1073/pnas.1614145114. Epub 2017 Mar 6.
3
The distinct functions of CENP-C and CENP-T/W in centromere propagation and function in Xenopus egg extracts.
Nucleus. 2015;6(2):133-43. doi: 10.1080/19491034.2014.1003509. Epub 2015 Jan 8.
4
Dynamic changes in CCAN organization through CENP-C during cell-cycle progression.
Mol Biol Cell. 2015 Nov 1;26(21):3768-76. doi: 10.1091/mbc.E15-07-0531. Epub 2015 Sep 9.
5
Specification of kinetochore-forming chromatin by the histone H3 variant CENP-A.
J Cell Sci. 2001 Oct;114(Pt 19):3529-42. doi: 10.1242/jcs.114.19.3529.
6
Independence of centromeric and pericentromeric chromatin stability on CCAN components.
Mol Biol Cell. 2025 Apr 1;36(4):ar41. doi: 10.1091/mbc.E24-02-0066. Epub 2025 Feb 12.
9
Induced ectopic kinetochore assembly bypasses the requirement for CENP-A nucleosomes.
Cell. 2011 Apr 29;145(3):410-22. doi: 10.1016/j.cell.2011.03.031.
10
Dynamics of CENP-N kinetochore binding during the cell cycle.
J Cell Sci. 2011 Nov 15;124(Pt 22):3871-83. doi: 10.1242/jcs.088625. Epub 2011 Nov 18.

引用本文的文献

1
A tribute to 40 years of CENP-A & centromere pioneer Bill Earnshaw.
Chromosoma. 2025 Jul 9;134(1):7. doi: 10.1007/s00412-025-00833-5.
2
Centromere-size reduction and chromatin state dynamics following intergenomic hybridization in cotton.
PLoS Genet. 2025 May 2;21(5):e1011689. doi: 10.1371/journal.pgen.1011689. eCollection 2025 May.
3
Emerging Roles for Transcription Factors During Mitosis.
Cells. 2025 Feb 12;14(4):263. doi: 10.3390/cells14040263.
4
A predictive chromatin architecture nexus regulates transcription and DNA damage repair.
J Biol Chem. 2025 Mar;301(3):108300. doi: 10.1016/j.jbc.2025.108300. Epub 2025 Feb 11.
5
Centromeric chromatin clearings demarcate the site of kinetochore formation.
Cell. 2025 Mar 6;188(5):1280-1296.e19. doi: 10.1016/j.cell.2024.12.025. Epub 2025 Jan 23.
6
High-resolution analysis of human centromeric chromatin.
Life Sci Alliance. 2025 Jan 23;8(4). doi: 10.26508/lsa.202402819. Print 2025 Apr.
7
Super-Resolution Imaging of Mitotic Spindle Microtubules Using STED Microscopy.
Methods Mol Biol. 2025;2872:3-19. doi: 10.1007/978-1-0716-4224-5_1.
8
Vertebrate centromere architecture: from chromatin threads to functional structures.
Chromosoma. 2024 Jul;133(3):169-181. doi: 10.1007/s00412-024-00823-z. Epub 2024 Jun 10.
9
Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin.
Cell. 2024 Jun 6;187(12):3006-3023.e26. doi: 10.1016/j.cell.2024.04.014. Epub 2024 May 13.
10
Centromeric chromatin clearings demarcate the site of kinetochore formation.
bioRxiv. 2024 Apr 26:2024.04.26.591177. doi: 10.1101/2024.04.26.591177.

本文引用的文献

1
A paucity of heterochromatin at functional human neocentromeres.
Epigenetics Chromatin. 2010 Mar 8;3(1):6. doi: 10.1186/1756-8935-3-6.
2
DNA binding of centromere protein C (CENPC) is stabilized by single-stranded RNA.
PLoS Genet. 2010 Feb 5;6(2):e1000835. doi: 10.1371/journal.pgen.1000835.
3
Cse4 is part of an octameric nucleosome in budding yeast.
Mol Cell. 2009 Sep 24;35(6):794-805. doi: 10.1016/j.molcel.2009.07.022.
5
The life and miracles of kinetochores.
EMBO J. 2009 Sep 2;28(17):2511-31. doi: 10.1038/emboj.2009.173. Epub 2009 Jul 23.
6
Dual color localization microscopy of cellular nanostructures.
Biotechnol J. 2009 Jun;4(6):927-38. doi: 10.1002/biot.200900005.
7
Centromere assembly requires the direct recognition of CENP-A nucleosomes by CENP-N.
Nat Cell Biol. 2009 Jul;11(7):896-902. doi: 10.1038/ncb1899. Epub 2009 Jun 21.
8
Protein architecture of the human kinetochore microtubule attachment site.
Cell. 2009 May 15;137(4):672-84. doi: 10.1016/j.cell.2009.03.035.
9
Condensin regulates the stiffness of vertebrate centromeres.
Mol Biol Cell. 2009 May;20(9):2371-80. doi: 10.1091/mbc.e08-11-1127. Epub 2009 Mar 4.
10
Putting super-resolution fluorescence microscopy to work.
Nat Methods. 2009 Jan;6(1):21-3. doi: 10.1038/nmeth.f.233.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验