TY - JOUR TI - Transcription of a 5’ extended mRNA isoform directs dynamic chromatin changes and interference of a downstream promoter AU - Chia, Minghao AU - Tresenrider, Amy AU - Chen, Jingxun AU - Spedale, Gianpiero AU - Jorgensen, Victoria AU - Ünal, Elçin AU - van Werven, Folkert Jacobus A2 - Keeney, Scott VL - 6 PY - 2017 DA - 2017/09/14 SP - e27420 C1 - eLife 2017;6:e27420 DO - 10.7554/eLife.27420 UR - https://doi.org/10.7554/eLife.27420 AB - Cell differentiation programs require dynamic regulation of gene expression. During meiotic prophase in Saccharomyces cerevisiae, expression of the kinetochore complex subunit Ndc80 is downregulated by a 5’ extended long undecoded NDC80 transcript isoform. Here we demonstrate a transcriptional interference mechanism that is responsible for inhibiting expression of the coding NDC80 mRNA isoform. Transcription from a distal NDC80 promoter directs Set1-dependent histone H3K4 dimethylation and Set2-dependent H3K36 trimethylation to establish a repressive chromatin state in the downstream canonical NDC80 promoter. As a consequence, NDC80 expression is repressed during meiotic prophase. The transcriptional mechanism described here is rapidly reversible, adaptable to fine-tune gene expression, and relies on Set2 and the Set3 histone deacetylase complex. Thus, expression of a 5’ extended mRNA isoform causes transcriptional interference at the downstream promoter. We demonstrate that this is an effective mechanism to promote dynamic changes in gene expression during cell differentiation. KW - transcription KW - chromatin KW - meiosis KW - interference KW - mRNA isoform KW - promoter JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -