engleski

Epigenetic control of transcription start site selection during mitotic growth and meiotic development.

The length of many transcripts changes when budding yeast and fission yeast cells exit mitosis and enter the meiotic developmental pathway and this can be attributed to variable untranslated regions (UTRs) notably at the 5’-end of mRNAs. However, a comprehensive approach to identifying developmentally regulated and meiosis-specific transcription start sites (TSSs) and transcription termination sites (TTSs) is lacking, and the mechanism governing the choice of TSSs during growth and development is unknown. Using genome-wide and DNA strand-specific RNA profiling, we observe pervasive variations of transcript start and termination sites during fermentation, respiration, and sporulation. The staggered onset of these mRNA variations corresponds to the transcriptional induction pattern shown by early and middle meiotic genes. We find that the histone deacetylase Rpd3 and its DNA binding subunit Ume6, which down-regulate meiotic genes in mitosis, play a novel role in the mitotic repression of cryptic meiotic TSSs. Given that many 5’-UTRs positively or negatively influence the translation of mRNAs, our results point to a novel epigenetic control mechanism for developmentally regulated protein expression. Since Rpd3 is highly conserved and ubiquitously expressed our findings are likely relevant for many developmental pathways in higher eukaryotes.

5'-UTRs; isoform; Rpd3

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