期刊
GENES & DEVELOPMENT
卷 32, 期 9-10, 页码 682-694出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.313973.118
关键词
nucleosome; transcription; gene expression; RNA polymerase II; chromatin dynamics
资金
- Deutsche Forschungsgemeinschaft [ME 4713/1-1]
- National Institutes of Health (NIH) grant [GM074207]
- Ludwig Institute for Cancer Research
- NIH/National Institute of Diabetes and Digestive and Kidney Diseases [DK091183]
- Foundation Le Ducq
- NIH/National Institute of General Medical Sciences [R35 GM118060]
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.
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