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Proc Natl Acad Sci U S A. 2015 Jul 7;112(27):8338-43. doi: 10.1073/pnas.1424705112. Epub 2015 Jun 22.

BEND3 represses rDNA transcription by stabilizing a NoRC component via USP21 deubiquitinase.

Author information

1
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
2
Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
3
Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801; Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801; Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
4
Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801; supriyap@life.illinois.edu.

Abstract

Ribosome biogenesis dictates the translational capacity of cells. Several mechanisms establish and maintain transcriptional output from eukaryotic ribosomal DNA (rDNA) loci. rDNA silencing is one such mechanism that ensures the inactivity and hence the maintenance of a silenced state of a subset of rRNA gene copies. Whereas oncogenic agents stimulate rRNA gene transcription, tumor suppressors decrease rRNA gene transcription. We demonstrate in mammalian cells that BANP, E5R, and Nac1 (BEN) domain 3 (BEND3), a quadruple BEN domain-containing protein, localizes in nucleoli and binds to ribosomal RNA gene promoters to help repress rRNA genes. Loss of BEND3 increases histone H3K4 trimethylation and, correspondingly, decreases rDNA promoter DNA methylation, consistent with a role for BEND3 in rDNA silencing. BEND3 associates with the nucleolar-remodeling complex (NoRC), and SUMOylated BEND3 stabilizes NoRC component TTF-1-interacting protein 5 via association with ubiquitin specific protease 21 (USP21) debiquitinase. Our results provide mechanistic insights into how the novel rDNA transcription repressor BEND3 acts together with NoRC to actively coordinate the establishment of rDNA silencing.

KEYWORDS:

BEND3; NoRC; Tip5; rDNA; transcription repression

PMID:
26100909
PMCID:
PMC4500215
DOI:
10.1073/pnas.1424705112
[Indexed for MEDLINE]
Free PMC Article

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