Cooke, SL;
Soares, BL;
Müller, CA;
Nieduszynski, CA;
Bastos de Oliveira, FM;
de Bruin, RAM;
(2021)
Tos4 mediates gene expression homeostasis through interaction with HDAC complexes independently of H3K56 acetylation.
Journal of Biological Chemistry
, 296
, Article 100533. 10.1016/j.jbc.2021.100533.
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Abstract
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.
Type: | Article |
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Title: | Tos4 mediates gene expression homeostasis through interaction with HDAC complexes independently of H3K56 acetylation |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1016/j.jbc.2021.100533 |
Publisher version: | https://doi.org/10.1016/j.jbc.2021.100533 |
Language: | English |
Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
URI: | https://discovery.ucl.ac.uk/id/eprint/10126764 |
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