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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Ventx1.1 competes with a transcriptional activator Xcad2 to regulate negatively its own expression

  • Kumar, Shiv (Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University) ;
  • Umair, Zobia (Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University) ;
  • Kumar, Vijay (Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University) ;
  • Lee, Unjoo (Department of Electrical Engineering, Hallym University) ;
  • Choi, Sun-Cheol (Department of Biomedical Sciences, University of Ulsan College of Medicine) ;
  • Kim, Jaebong (Department of Biochemistry, Institute of Cell Differentiation and Aging, College of Medicine, Hallym University)
  • Received : 2019.03.26
  • Accepted : 2019.04.18
  • Published : 2019.06.30
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Abstract

Dorsoventral patterning of body axis in vertebrate embryo 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, competitively co-occupied the VRE in the Ventx1.1 promoter. In support of this, mutation of the VRE down-regulated basal and 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. Taken together, these results suggest that Ventx1.1 negatively regulates its own transcription in competition with Xcad2, thereby fine-tuning its own expression levels during dorsoventral patterning of Xenopus early embryo.

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References

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