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Elife. 2017 Sep 14;6. pii: e27420. doi: 10.7554/eLife.27420.

Transcription of a 5' extended mRNA isoform directs dynamic chromatin changes and interference of a downstream promoter.

Author information

1
The Francis Crick Institute, London, United Kingdom.
2
Department of Molecular and Cell Biology, University of California, Berkeley, 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.

KEYWORDS:

S. cerevisiae; chromatin; chromosomes; genes; interference; mRNA isoform; meiosis; promoter; transcription

PMID:
28906248
PMCID:
PMC5655139
DOI:
10.7554/eLife.27420
[Indexed for MEDLINE]
Free PMC Article

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