The conserved histone deacetylase Rpd3 and its DNA binding subunit Ume6 control dynamic transcript architecture during mitotic growth and meiotic development.

It was recently reported that the sizes of many mRNAs change when budding yeast cells exit mitosis and enter the meiotic differentiation pathway. These differences were attributed to length variations of their untranslated regions. The function of UTRs in protein translation is well established. However, the mechanism controlling the expression of distinct transcript isoforms during mitotic growth and meiotic development is unknown. In this study, we order developmentally regulated transcript isoforms according to their expression at specific stages during meiosis and gametogenesis, as compared to vegetative growth and starvation. We employ regulatory motif prediction, in vivo protein-DNA binding assays, genetic analyses and monitoring of epigenetic amino acid modification patterns to identify a novel role for Rpd3 and Ume6, two components of a histone deacetylase complex already known to repress early meiosis-specific genes in dividing cells, in mitotic repression of meiosis-specific transcript isoforms. Our findings classify developmental stage-specific early, middle and late meiotic transcript isoforms, and they point to a novel HDAC-dependent control mechanism for flexible transcript architecture during cell growth and differentiation. Since Rpd3 is highly conserved and ubiquitously expressed in many tissues, our results are likely relevant for development and disease in higher eukaryotes.

Lardenois A ，Stuparevic I ，Liu Y ，Law MJ ，Becker E ，Smagulova F ，Waern K ，Guilleux MH ，Horecka J ，Chu A ，Kervarrec C ，Strich R ，Snyder M ，Davis RW ，Steinmetz LM ，Primig M ... -  《-》

The conserved histone deacetylase Rpd3 and the DNA binding regulator Ume6 repress BOI1's meiotic transcript isoform during vegetative growth in Saccharomyces cerevisiae.

BOI1 and BOI2 are paralogs important for the actin cytoskeleton and polar growth. BOI1 encodes a meiotic transcript isoform with an extended 5'-untranslated region predicted to impair protein translation. It is, however, unknown how the isoform is repressed during mitosis, and if Boi1 is present during sporulation. By interpreting microarray data from MATa cells, MATa/α cells, a starving MATα/α control, and a meiosis-impaired rrp6 mutant, we classified BOI1's extended isoform as early meiosis-specific. These results were confirmed by RNA-Sequencing, and extended by a 5'-RACE assay and Northern blotting, showing that meiotic cells induce the long isoform while the mitotic isoform remains detectable during meiosis. We provide evidence via motif predictions, an in vivo binding assay and genetic experiments that the Rpd3/Sin3/Ume6 histone deacetylase complex, which represses meiotic genes during mitosis, also prevents the induction of BOI1's 5'-extended isoform in mitosis by direct binding of Ume6 to its URS1 target. Finally, we find that Boi1 protein levels decline when cells switch from fermentation to respiration and sporulation. The histone deacetylase Rpd3 is conserved, and eukaryotic genes frequently encode transcripts with variable 5'-UTRs. Our findings are therefore relevant for regulatory mechanisms involved in the control of transcript isoforms in multi-cellular organisms.

Liu Y ，Stuparevic I ，Xie B ，Becker E ，Law MJ ，Primig M ... -  《-》

The histone deacetylase Rpd3/Sin3/Ume6 complex represses an acetate-inducible isoform of VTH2 in fermenting budding yeast cells.

The tripartite Rpd3/Sin3/Ume6 complex represses meiotic isoforms during mitosis. We asked if it also controls starvation-induced isoforms. We report that VTH1/VTH2 encode acetate-inducible isoforms with extended 5'-regions overlapping antisense long non-coding RNAs. Rpd3 and Ume6 repress the long isoform of VTH2 during fermentation. Cells metabolising glucose contain Vth2, while the protein is undetectable in acetate and during sporulation. VTH2 is a useful model locus to study mechanisms implicating promoter directionality, lncRNA transcription and post-transcriptional control of gene expression via 5'-UTRs. Since mammalian genes encode transcript isoforms and Rpd3 is conserved, our findings are relevant for gene expression in higher eukaryotes.

Stuparevic I ，Becker E ，Law MJ ，Primig M ... -  《-》

Ndt80 activates the meiotic ORC1 transcript isoform and SMA2 via a bi-directional middle sporulation element in Saccharomyces cerevisiae.

Xie B ，Horecka J ，Chu A ，Davis RW ，Becker E ，Primig M ... -  《-》

Global alterations of the transcriptional landscape during yeast growth and development in the absence of Ume6-dependent chromatin modification.

Lardenois A ，Becker E ，Walther T ，Law MJ ，Xie B ，Demougin P ，Strich R ，Primig M ... -  《-》