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PLoS One. 2014 Jul 1;9(7):e101151. doi: 10.1371/journal.pone.0101151. eCollection 2014.

Miz-1 activates gene expression via a novel consensus DNA binding motif.

Author information

1
Department of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Davis, California, United States of America; Genome Center, University of California Davis, Davis, California, United States of America; Comprehensive Cancer Center, University of California Davis, Sacramento, California, United States of America; Institute of Pediatric Regenerative Medicine, Shriners Hospital For Children Northern California, Sacramento, California, United States of America.
2
Genome Center, University of California Davis, Davis, California, United States of America; Department of Biochemistry, University of California Davis, Davis, California, United States of America.

Erratum in

  • PLoS One. 2014;9(9):e108565.

Abstract

The transcription factor Miz-1 can either activate or repress gene expression in concert with binding partners including the Myc oncoprotein. The genomic binding of Miz-1 includes both core promoters and more distal sites, but the preferred DNA binding motif of Miz-1 has been unclear. We used a high-throughput in vitro technique, Bind-n-Seq, to identify two Miz-1 consensus DNA binding motif sequences--ATCGGTAATC and ATCGAT (Mizm1 and Mizm2)--bound by full-length Miz-1 and its zinc finger domain, respectively. We validated these sequences directly as high affinity Miz-1 binding motifs. Competition assays using mutant probes indicated that the binding affinity of Miz-1 for Mizm1 and Mizm2 is highly sequence-specific. Miz-1 strongly activates gene expression through the motifs in a Myc-independent manner. MEME-ChIP analysis of Miz-1 ChIP-seq data in two different cell types reveals a long motif with a central core sequence highly similar to the Mizm1 motif identified by Bind-n-Seq, validating the in vivo relevance of the findings. Miz-1 ChIP-seq peaks containing the long motif are predominantly located outside of proximal promoter regions, in contrast to peaks without the motif, which are highly concentrated within 1.5 kb of the nearest transcription start site. Overall, our results indicate that Miz-1 may be directed in vivo to the novel motif sequences we have identified, where it can recruit its specific binding partners to control gene expression and ultimately regulate cell fate.

PMID:
24983942
PMCID:
PMC4077741
DOI:
10.1371/journal.pone.0101151
[Indexed for MEDLINE]
Free PMC Article
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