2. Academic Validation
  3. NDF, a nucleosome-destabilizing factor that facilitates transcription through nucleosomes

NDF, a nucleosome-destabilizing factor that facilitates transcription through nucleosomes

  • Genes Dev. 2018 May 1;32(9-10):682-694. doi: 10.1101/gad.313973.118.
Jia Fei 1,  Haruhiko Ishii 2,  Marten A Hoeksema 3 4,  Franz Meitinger 2,  George A Kassavetis 1,  Christopher K Glass 3 4,  Bing Ren 2 3 5,  James T Kadonaga 1
Affiliations

Affiliations

  • 1 Section of Molecular Biology, University of California at San Diego, La Jolla, California 92093, USA.
  • 2 Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, California 92093, USA.
  • 3 Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093, USA.
  • 4 Department of Medicine, University of California at San Diego, La Jolla, California 92093, USA.
  • 5 Center for Epigenomics, Institute of Genome Medicine, Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA.
PMID: 29759984 DOI: 10.1101/gad.313973.118
Abstract

Our understanding of transcription by RNA polymerase II (Pol II) is limited by our knowledge of the factors that mediate this critically important process. Here we describe the identification of NDF, a nucleosome-destabilizing factor that facilitates Pol II transcription in chromatin. NDF has a PWWP motif, interacts with nucleosomes near the dyad, destabilizes nucleosomes in an ATP-independent manner, and facilitates transcription by Pol II through nucleosomes in a purified and defined transcription system as well as in cell nuclei. Upon transcriptional induction, NDF is recruited to the transcribed regions of thousands of genes and colocalizes with a subset of H3K36me3-enriched regions. Notably, the recruitment of NDF to gene bodies is accompanied by an increase in the transcript levels of many of the NDF-enriched genes. In addition, the global loss of NDF results in a decrease in the RNA levels of many genes. In humans, NDF is present at high levels in all tested tissue types, is essential in stem cells, and is frequently overexpressed in breast Cancer. These findings indicate that NDF is a nucleosome-destabilizing factor that is recruited to gene bodies during transcriptional activation and facilitates Pol II transcription through nucleosomes.

Keywords

RNA polymerase II; chromatin dynamics; gene expression; nucleosome; transcription.

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