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

Tutkimustuotos: ArtikkeliTieteellinenvertaisarvioitu

1 Sitaatiot (Scopus)
17 Lataukset (Pure)

Abstrakti

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.

AlkuperäiskieliEnglanti
Artikkeli194811
Sivumäärä9
JulkaisuBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Vuosikerta1865
Numero3
DOI - pysyväislinkit
TilaJulkaistu - huhtik. 2022
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Rahoitus

This work was supported by Jenny and Antti Wihuri Foundation, Finland (E.M.V.), Finnish Cultural Foundation?s Pirkanmaa regional fund, Finland (A.R-M., E.M.V., J.U-M.), Academy of Finland, Finland project no. 312043 and 310829 (M.N.), Cancer Society of Finland, Finland (M.N., A.K.) This work was supported by Jenny and Antti Wihuri Foundation , Finland (E.M.V.), Finnish Cultural Foundation´s Pirkanmaa regional fund, Finland (A.R-M., E.M.V., J.U-M.), Academy of Finland , Finland project no. 312043 and 310829 (M.N.), Cancer Society of Finland , Finland (M.N., A.K.)

Julkaisufoorumi-taso

  • Jufo-taso 1

!!ASJC Scopus subject areas

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

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