Transcription of a 5' extended mRNA isoform directs dynamic chromatin changes and interference of a downstream promoter
- The Francis Crick Institute, United Kingdom
- University of California, Berkeley, United States
Abstract
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.
Article and author information
Author details
Folkert Jacobus van Werven
Funding
Francis Crick Institute (FC001203)
- Folkert Jacobus van Werven
Pew Charitable Trusts (27344)
- Elçin Ünal
Glenn Foundation for Medical Research
- Elçin Ünal
March of Dimes Foundation (5-FY15-99)
- Elçin Ünal
National Science Foundation (DGE-1106400 Graduate Student Fellowship)
- Jingxun Chen
- Elçin Ünal
Agency for Science, Technology and Research (Graduate Student Fellowship)
- Minghao Chia
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Chia et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Transcription of a 5' extended mRNA isoform directs dynamic chromatin changes and interference of a downstream promoter
eLife 6:e27420.
https://doi.org/10.7554/eLife.27420
Further reading
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A key protein involved in the segregation of meiotic chromosomes is produced 'just in time' by the regulated expression of two mRNA isoforms.
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