Research Papers: Chromosome:

ZSCAN5B and primate-specific paralogs bind RNA polymerase III genes and extra-TFIIIC (ETC) sites to modulate mitotic progression

Younguk Sun, Huimin Zhang, Majid Kazemian, Joseph M. Troy, Christopher Seward, Xiaochen Lu and Lisa Stubbs _

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Oncotarget. 2016; 7:72571-72592. https://doi.org/10.18632/oncotarget.12508

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Younguk Sun1,2, Huimin Zhang1,2, Majid Kazemian1,4, Joseph M. Troy1,3, Christopher Seward1,2, Xiaochen Lu1,2 and Lisa Stubbs1,2

1 Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA

2 Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL, USA

3 Illinois Informatics Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA

4 Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

Correspondence to:

Lisa Stubbs, email:

Keywords: zinc finger transcription factor, primate-specific duplication, RNA Polymerase III transcription, chromatin architecture, cell cycle, Chromosome Section

Received: August 13, 2016 Accepted: September 20, 2016 Published: October 06, 2016


Mammalian genomes contain hundreds of genes transcribed by RNA Polymerase III (Pol III), encoding noncoding RNAs and especially the tRNAs specialized to carry specific amino acids to the ribosome for protein synthesis. In addition to this well-known function, tRNAs and their genes (tDNAs) serve a variety of other critical cellular functions. For example, tRNAs and other Pol III transcripts can be cleaved to yield small RNAs with potent regulatory activities. Furthermore, from yeast to mammals, active tDNAs and related “extra-TFIIIC” (ETC) loci provide the DNA scaffolds for the most ancient known mechanism of three-dimensional chromatin architecture. Here we identify the ZSCAN5 TF family - including mammalian ZSCAN5B and its primate-specific paralogs - as proteins that occupy mammalian Pol III promoters and ETC sites. We show that ZSCAN5B binds with high specificity to a conserved subset of Pol III genes in human and mouse. Furthermore, primate-specific ZSCAN5A and ZSCAN5D also bind Pol III genes, although ZSCAN5D preferentially localizes to MIR SINE- and LINE2-associated ETC sites. ZSCAN5 genes are expressed in proliferating cell populations and are cell-cycle regulated, and siRNA knockdown experiments suggested a cooperative role in regulation of mitotic progression. Consistent with this prediction, ZSCAN5A knockdown led to increasing numbers of cells in mitosis and the appearance of cells. Together, these data implicate the role of ZSCAN5 genes in regulation of Pol III genes and nearby Pol II loci, ultimately influencing cell cycle progression and differentiation in a variety of tissues.

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