Specific functions for the fission yeast Sirtuins Hst2 and Hst4 in gene regulation and retrotransposon silencing.
Expression profiling, ChiP-CHIP and phenotypic analysis were used to investigate the functional relationships of class III NAD(+)-dependent HDACs (Sirtuins) in fission yeast. We detected significant histone acetylation increases in Sirtuin mutants at their specific genomic binding targets and were thus able to identify an in vivo substrate preference for each Sirtuin. At heterochromatic loci, we demonstrate that although Hst2 is mainly cytoplasmic, a nuclear pool of Hst2 colocalizes with the other Sirtuins at silent regions (cen, mat, tel, rDNA), and that like the other Sirtuins, Hst2 is required for rDNA and centromeric silencing. Interestingly we found specific functions for the fission yeast Sirtuins Hst2 and Hst4 in gene regulation. Hst2 directly represses genes involved in transport and membrane function, whereas Hst4 represses amino-acid biosynthesis genes and Tf2 retrotransposons. A specific role for Hst4 in Tf2 5' mRNA processing was revealed. Thus, Sirtuins share functions at many genomic targets, but Hst2 and Hst4 have also evolved unique functions in gene regulation.
Durand-Dubief
Mickaël
M
Karolinska Institutet, Department of Biosciences/School of Life Sciences, University College Södertörn, Huddinge, Sweden.
Sinha
Indranil
I
Fagerström-Billai
Fredrik
F
Bonilla
Carolina
C
Wright
Anthony
A
Grunstein
Michael
M
Ekwall
Karl
K
D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D005800:Genes, Fungal; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D018626:Retroelements; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics* / Q000378:metabolism; D013379:Substrate Specificity
D018626:Retroelements; D029701:Saccharomyces cerevisiae Proteins; C423033:HST2 protein, S cerevisiae; C512518:Hst4 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases