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

Jia Fei, Haruhiko Ishii, Marten A. Hoeksema, Franz Meitinger, George A. Kassavetis, Christopher K. Glass, Bing Ren, James T. Kadonaga

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)682-694
Number of pages13
JournalGenes and Development
Volume32
Issue number9-10
DOIs
StatePublished - May 1 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

Keywords

  • Chromatin dynamics
  • Gene expression
  • Nucleosome
  • RNA polymerase II
  • Transcription

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