Novel ZNF414 activity characterized by integrative analysis of ChIP-exo, ATAC-seq and RNA-seq data

Alejandra Rodriguez-Martinez, Elisa M. Vuorinen, Anastasia Shcherban, Joonas Uusi-Mäkelä, Nina K.M. Rajala, Matti Nykter, Anne Kallioniemi

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Abstract

Transcription factor binding to DNA is a central mechanism regulating gene expression. Thus, thorough characterization of this process is essential for understanding cellular biology in both health and disease. We combined data from three sequencing-based methods to unravel the DNA binding function of the novel ZNF414 protein in cells representing two tumor types. ChIP-exo served to map protein binding sites, ATAC-seq allowed identification of open chromatin, and RNA-seq examined the transcriptome. We show that ZNF414 is a DNA-binding protein that both induces and represses gene expression. This transcriptional response has an impact on cellular processes related to proliferation and other malignancy-associated functions, such as cell migration and DNA repair. Approximately 20% of the differentially expressed genes harbored ZNF414 binding sites in their promoters in accessible chromatin, likely representing direct targets of ZNF414. De novo motif discovery revealed several putative ZNF414 binding sequences, one of which was validated using EMSA. In conclusion, this study illustrates a highly efficient integrative approach for the characterization of the DNA binding and transcriptional activity of transcription factors.

Original languageEnglish
Article number194811
Number of pages9
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1865
Issue number3
DOIs
Publication statusPublished - Apr 2022
Publication typeA1 Journal article-refereed

Keywords

  • ATAC-seq
  • ChIP-exo
  • Gene regulation
  • Transcription factor
  • ZNF414

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics

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