Transcription of a 5' extended mRNA isoform directs dynamic chromatin changes and interference of a downstream promoterMore about Open Access at the Crick
Authors listMinghao Chia Amy Tresenrider Jingxun Chen Gianpiero Spedale Victoria Jorgensen Elçin Ünal Folkert Van Werven
Cell differentiation programs require dynamic regulation of gene expression. During meiotic prophase in , expression of the kinetochore complex subunit Ndc80 is downregulated by a 5' extended long undecoded transcript isoform. Here we demonstrate a transcriptional interference mechanism that is responsible for inhibiting expression of the coding mRNA isoform. Transcription from a distal promoter directs Set1-dependent histone H3K4 dimethylation and Set2-dependent H3K36 trimethylation to establish a repressive chromatin state in the downstream canonical promoter. As a consequence, 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.