Huning, Laura Elizabeth (2020-08). Transcriptional Activation of Eukaryotic Promoters via Zinc Finger Protein 143. Doctoral Dissertation. Thesis uri icon

abstract

  • Zinc Finger Protein 143 (ZNF143) is a ubiquitous C2H2 zinc-finger transcriptional activator in vertebrates. Predicted to regulate over 2000 promoters, ZNF143 activates transcription at both protein coding genes and small RNA genes transcribed by either RNA polymerase II or RNA polymerase III. Recently, an auxiliary function for ZNF143 as an architectural factor localizing at chromatin interactions has emerged. Promoters targeted for activation by ZNF143 are functionally diverse, involving many cellular processes such as cell cycle regulation, cancer, and development. The zebrafish genome contains a previously uncharacterized paralog of znf143b, znf143a, that contributes to the overall function as an activator in zebrafish. To identify the contribution of activator function of ZNF143a to the overall activation by ZNF143, this dissertation involves an expression analysis and targeted knockdown of each paralog in zebrafish. This dissertation demonstrates ZNF143a as a highly similar activator protein, however differentially expressed in the early development of zebrafish. Furthermore, the use of paralog specific knockdowns of each paralog presents developmental defects in the brain of 24hour embryos. Additionally, the molecular mechanism by which ZNF143 activates small RNA and mRNA encoding target genes is unknown. To investigate the mechanism of ZNF143, transgenic zebrafish lines were constructed to determine any potential architectural features that distinguish promoters regulated by ZNF143. Preliminary results suggest that positive histone modifications are present at promoters containing SPH sites and reduced at promoter regions containing a mutated SPH site.

ETD Chair

  • Bryk, Mary  Associate Professor and Associate Dean for Academic Affairs, College of Agriculture and Life Sciences

publication date

  • December 2020
  • December 2020
  • December 2020
  • December 2020
  • August 2020
  • December 2020