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

Official URL:https://doi.org/10.1016/j.molcel.2013.06.002
PubMed:View item in PubMed
Creators Name:Cecere, G. and Hoersch, S. and Jensen, M.B. and Dixit, S. and Grishok, A.
Journal Title:Molecular Cell
Journal Abbreviation:Mol Cell
Volume:50
Number:6
Page Range:894-907
Date:27 June 2013
Keywords:Caenorhabditis Elegans, Caenorhabditis Elegans Proteins, Chromatin Immunoprecipitation, DNA Polymerase II, Gene Expression Regulation, Gene Knockdown Techniques, Genetic Promoter Regions, Genetic Transcription, Heat-Shock Response, Helminth Genes, Histone-Lysine N-Methyltransferase, Histones, Protein Transport, RNA Interference, Transcription Factors, Ubiquitination, Animals
Abstract: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.
ISSN:1097-2765
Publisher:Cell Press (U.S.A.)
Item Type:Article

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