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Fkh1 and Fkh2 associate with Sir2 to control CLB2 transcription under normal and oxidative stress conditions

Linke, C., Klipp, E., Lehrach, H., Barberis, Matteo and Krobitsch, S. (2013) Fkh1 and Fkh2 associate with Sir2 to control CLB2 transcription under normal and oxidative stress conditions Frontiers in Physiology, 4, 173.

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Abstract

The Forkhead (Fkh) box family of transcription factors is evolutionary conserved from yeast to higher eukaryotes and its members are involved in many physiological processes including metabolism, DNA repair, cell cycle, stress resistance, apoptosis, and aging. In budding yeast, four Fkh transcription factors were identified, namely Fkh1, Fkh2, Fhl1, and Hcm1, which are implicated in chromatin silencing, cell cycle regulation, and stress response. These factors impinge transcriptional regulation during cell cycle progression, and histone deacetylases (HDACs) play an essential role in this process, e.g., the nuclear localization of Hcm1 depends on Sir2 activity, whereas Sin3/Rpd3 silence cell cycle specific gene transcription in G2/M phase. However, a direct involvement of Sir2 in Fkh1/Fkh2-dependent regulation of target genes is at present unknown. Here, we show that Fkh1 and Fkh2 associate with Sir2 in G1 and M phase, and that Fkh1/Fkh2-mediated activation of reporter genes is antagonized by Sir2. We further report that Sir2 overexpression strongly affects cell growth in an Fkh1/Fkh2-dependent manner. In addition, Sir2 regulates the expression of the mitotic cyclin Clb2 through Fkh1/Fkh2-mediated binding to the CLB2 promoter in G1 and M phase. We finally demonstrate that Sir2 is also enriched at the CLB2 promoter under stress conditions, and that the nuclear localization of Sir2 is dependent on Fkh1 and Fkh2. Taken together, our results show a functional interplay between Fkh1/Fkh2 and Sir2 suggesting a novel mechanism of cell cycle repression. Thus, in budding yeast, not only the regulation of G2/M gene expression but also the protective response against stress could be directly coordinated by Fkh1 and Fkh2. © 2013 Linke, Klipp, Lehrach, Barberis and Krobitsch.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Linke, C.
Klipp, E.
Lehrach, H.
Barberis, Matteom.barberis@surrey.ac.uk
Krobitsch, S.
Date : 12 July 2013
Funders : European Commission, ENFIN
DOI : 10.3389/fphys.2013.00173
Copyright Disclaimer : © 2013 Linke, Klipp, Lehrach, Barberis and Krobitsch. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
Uncontrolled Keywords : Budding yeast; Cell cycle; Fkh1; Fkh2; Silencing; Sir2; Stress
Depositing User : Clive Harris
Date Deposited : 15 Apr 2019 12:46
Last Modified : 15 Apr 2019 12:46
URI: http://epubs.surrey.ac.uk/id/eprint/851015

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