Tos4 mediates gene expression homeostasis through interaction with HDAC complexes independently of H3K56 acetylation

Cooke, Sophie L., Soares, Barbara L., Müller, Carolin A., Nieduszynski, Conrad A. ORCID:, Bastos de Oliveira, Francisco M. and de Bruin, Robertus A. M. (2021) Tos4 mediates gene expression homeostasis through interaction with HDAC complexes independently of H3K56 acetylation. Journal of Biological Chemistry, 296. ISSN 0021-9258

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Saccharomyces cerevisiae exhibits gene expression homeostasis, which is defined as the buffering of transcription levels against changes in DNA copy number during the S phase of the cell cycle. It has been suggested that S. cerevisiae employs an active mechanism to maintain gene expression homeostasis through Rtt109-Asf1-dependent acetylation of histone H3 on lysine 56 (H3K56). Here, we show that gene expression homeostasis can be achieved independently of H3K56 acetylation by Tos4 (Target of Swi6-4). Using Nanostring technology, we establish that Tos4-dependent gene expression homeostasis depends on its forkhead-associated (FHA) domain, which is a phosphopeptide recognition domain required to bind histone deacetylases (HDACs). We demonstrate that the mechanism of Tos4-dependent gene expression homeostasis requires its interaction with the Rpd3L HDAC complex. However, this is independent of Rpd3's well-established roles in both histone deacetylation and controlling the DNA replication timing program, as established by deep sequencing of Fluorescence- Activated Cell Sorted (FACS) S and G2 phase populations. Overall, our data reveals that Tos4 mediates gene expression homeostasis through its FHA domain-dependent interaction with the Rpd3L complex, which is independent of H3K56ac.

Item Type: Article
Additional Information: Funding Information: This work was supported by core funding to the MRC-UCL University Unit (Ref. MC_EX_G0800785) and funded by R. A. M. d. B.’s Cancer Research UK Programme Foundation Award, F. M. B. d. O. is funded by FAPERJ E-26/010.002425/2019, E-26/26/010.002187/ 2019 and B. L. S. is supported by a scholarship from CAPES/PRINT 41/2017.
Uncontrolled Keywords: biochemistry,molecular biology,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1303
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 07 Sep 2022 14:31
Last Modified: 21 Oct 2022 01:37
DOI: 10.1016/j.jbc.2021.100533

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