Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2022 Jul 21;33(9):br15. doi: 10.1091/mbc.E21-06-0283

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© 2022 Niedzialkowska et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.

This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial-Share Alike 4.0 International Creative Commons License.

PMC Copyright notice

FIGURE 6: — Inhibition of Tip60 promotes premature centromeric targeting of Aurora B in interphase cells. (A) Inhibition of Tip60 by Nu9056 leads to Aurora B localization at centromeres in interphase (S/G2) cells as shown by immunofluorescence; scale bar, 20 µm. (B) Quantification of S/G2 centromeric fluorescence signals for Aurora B in control cells (n = 9, 26) and in Tip60-inhibited cells (n = 26, 23) p value (2.833⋅10^–7, 8.152⋅10^–5). Aurora B signal that overlaps with an ACA mask was quantified in S/G2 cells as defined by Aurora B signal. G1 cells have low Aurora B signal since Aurora B is an APC substrate. For statistical analysis Welch’s t test was applied. ***P < 0.001. (C) A proposed model for Aurora B localization regulated by acetylation of H3K4 of H3 by Tip60. Our data suggest that histone H3K4ac by Tip60 during S/G2 prevents Haspin phosphorylation of H3T3 (arrow a) and Survivin binding to chromatin to inhibit CPC localization to centromeres (arrow c). During the middle of prophase HDAC3 removes H3K4ac mark to enable CPC accumulation at inner centromeres. Previous studies have shown that Tip60 inhibits Bub1 binding to H2AT120 (arrow b) (Lee et al., 2018) and together with our work it suggests that Tip60 is a master regulator of CPC localization. (D) A model to control the timing of CPC localization to inner centromeres through changes in chromatin PTMs. Tip60 acetylates histone H3 on K4 and histone H2A on K118 in S/G2 to prevent CPC localization. In midprophase HDAC1 and HDAC3 deacetylate these histone marks to enable Bub1 phosphorylation and subsequent Sgo1 recruitment, Haspin phosphorylation of histone H3T3 and subsequent Survivin binding of H3T3ph. Together these events drive CPC recruitment to inner centromeres in midprophase.