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

Mol Cell. 2013 Jun 27;50(6):894-907. doi: 10.1016/j.molcel.2013.06.002.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • Chromatin Immunoprecipitation
  • DNA Polymerase II / genetics*
  • DNA Polymerase II / metabolism
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Genes, Helminth
  • Heat-Shock Response
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histones / metabolism*
  • Promoter Regions, Genetic
  • Protein Transport
  • RNA Interference
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Ubiquitination*


  • Caenorhabditis elegans Proteins
  • Histones
  • Transcription Factors
  • Zfp-1 protein, C elegans
  • DOT-1.1 protein, C elegans
  • Histone-Lysine N-Methyltransferase
  • DNA Polymerase II

Associated data

  • GEO/GSE47132