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

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

Blog Article

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 HERBATINT FF6 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 Hub Flywheel 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.