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© Germano Cecere, Institut Pasteur
Publication : Molecular cell

The ZFP-1(AF10)/DOT-1 complex opposes H2B ubiquitination to reduce Pol II transcription

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Molecular cell - 27 Jun 2013

Cecere G, Hoersch S, Jensen MB, Dixit S, Grishok A

Link to Pubmed [PMID] – 23806335

Mol. Cell 2013 Jun;50(6):894-907

The inhibition of transcriptional elongation plays an important role in gene regulation in metazoans, including C. elegans. Here, we combine genomic and biochemical approaches to dissect a role of ZFP-1, the C. elegans AF10 homolog, in transcriptional control. We show that ZFP-1 and its interacting partner DOT-1.1 have a global role in negatively modulating the level of polymerase II (Pol II) transcription on essential widely expressed genes. Moreover, the ZFP-1/DOT-1.1 complex contributes to progressive Pol II pausing on essential genes during development and to rapid Pol II pausing during stress response. The slowing down of Pol II transcription by ZFP-1/DOT-1.1 is associated with an increase in H3K79 methylation and a decrease in H2B monoubiquitination, which promotes transcription. We propose a model wherein the recruitment of ZFP-1/DOT-1.1 and deposition of H3K79 methylation at highly expressed genes initiates a negative feedback mechanism for the modulation of their expression.