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Ventx1.1 competes with a transcriptional activator Xcad2 to regulate negatively its own expression
Shiv Kumar1, Zobia Umair1, Vijay Kumar1, Unjoo Lee2, Sun-Cheol Choi3,*,#, Jaebong Kim1,#
1Department of Biochemistry, College of Medicine, Hallym University,
2Department of Electrical Engineering, Hallym University,
3Department of Biomedical Sciences, University of Ulsan College of Medicine
Abstract
In vertebrate embryo, the dorsoventral patterning of body axis is tightly controlled by a complex regulatory network of transcription factors. Ventx1.1 is known as a transcriptional repressor to inhibit dorsal mesoderm formation and neural differentiation in Xenopus. In an attempt to identify, using chromatin immunoprecipitation (ChIP)-Seq, genome-wide binding pattern of Ventx1.1 in Xenopus gastrulae, we observed that Ventx1.1 associates with its own 5'-flanking sequence. In this study, we present evidence that Ventx1.1 binds a cis-acting Ventx1.1 response element (VRE) in its own promoter, leading to repression of its own transcription. Site-directed mutagenesis of the VRE in the Ventx1.1 promoter significantly abrogated this inhibitory autoregulation of Ventx1.1 transcription. Notably, Ventx1.1 and Xcad2, an activator of Ventx1.1 transcription, co-occupied competitively the VRE in the Ventx1.1 promoter. In support of this, mutation of the VRE down-regulated the basal as well as Xcad2-induced levels of Ventx1.1 promoter activity. In addition, overexpression of Ventx1.1 prevented Xcad2 from binding to the Ventx1.1 promoter, and vice versa. Together, these results suggest that Ventx1.1 negatively regulates its own transcription in competition with Xcad2, thereby fine-tuning its own expression levels during the dorsoventral patterning of Xenopus early embryo.
Abstract, Accepted Manuscript(in press) [Submitted on March 26, 2019, Accepted on April 18, 2019]
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