Abstract
In fission yeast, the ste11 gene encodes the master regulator initiating the switch from vegetative growth to gametogenesis. In a previous paper, we showed that the methylation of H3K4 and consequent promoter nucleosome deacetylation repress ste11 induction and cell differentiation (Materne et al., 2015) but the regulatory steps remain poorly understood. Here we report a genetic screen that highlighted H2B deubiquitylation and the RSC remodeling complex as activators of ste11 expression. Mechanistic analyses revealed more complex, opposite roles of H2Bubi at the promoter where it represses expression, and over the transcribed region where it sustains it. By promoting H3K4 methylation at the promoter, H2Bubi initiates the deacetylation process, which decreases chromatin remodeling by RSC. Upon induction, this process is reversed and efficient NDR (nucleosome depleted region) formation leads to high expression. Therefore, H2Bubi represses gametogenesis by opposing the recruitment of RSC at the promoter of the master regulator ste11 gene.
Highlights
The RNA polymerase II (PolII) subunit Rpb1 C-terminal Domain shows a stereotypical pattern of CTD phosphorylation with phospho-S5 (S5P) peaking near the transcription start site (TSS) and phosphoS2 (S2P) accumulating towards the 3’-end of the transcribed region (Buratowski, 2009; Cassart et al, 2012; Drogat and Hermand, 2012)
The overexpression of cdc14 significantly suppresses the latrunculin A (LatA) sensitivity of a strain deleted for lsk1 (Figure 1—figure supplement 1A,B), supporting that the LatA sensitivity of the lsk1 mutant relates to the downregulation of cdc14
Despite the fact that the phosphorylation of the CTD S2 is not essential in yeast, the master regulator of gametogenesis, ste11, requires an unusual requirement of S2P nearby its promoter for proper induction to counteract the repressed state imposed by the Set1-H3K4me3-HDAC pathway (Materne et al, 2015)
Summary
The RNA polymerase II (PolII) subunit Rpb C-terminal Domain shows a stereotypical pattern of CTD phosphorylation with phospho-S5 (S5P) peaking near the transcription start site (TSS) and phosphoS2 (S2P) accumulating towards the 3’-end of the transcribed region (Buratowski, 2009; Cassart et al, 2012; Drogat and Hermand, 2012). The distribution of histone H3 lysine 4 methylation (H3K4me) mirrors S5P due to the direct recruitment of the H3 methyltransferase Set1-COMPASS by the S5P of PolII (Keogh et al, 2005; Ng et al, 2003). Most genes are upregulated in fission yeast when Set is absent (Lorenz et al, 2014). The PHD finger protein Set, which is part of the SET3C HDAC complex, binds H3K4me to mediate deacetylation of histones in the 5’ regions (Kim and Buratowski, 2009; Kim et al, 2012). The PHD domain of the HDAC-associated ING2 protein mediates its binding to the di- and trimethylated H3K4 at the promoters of proliferation genes (Pena et al, 2006; Shi et al, 2006)
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