Transcription factors Krüppel-like factor 4 and paired box 5 regulate the expression of the Grainyhead-like genes.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Gene Expression Regulation*; Kruppel-Like Transcription Factors/*physiology ; PAX5 Transcription Factor/*physiology ; Transcription Factors/*metabolism; Animals ; Chromatin Immunoprecipitation ; Computer Simulation ; DNA-Binding Proteins/metabolism ; Electrophoretic Mobility Shift Assay ; Gene Frequency ; HEK293 Cells ; Humans ; Kruppel-Like Factor 4 ; Kruppel-Like Transcription Factors/genetics ; Mice ; PAX5 Transcription Factor/metabolism ; Polymorphism, Single Nucleotide/genetics ; Real-Time Polymerase Chain Reaction ; Repressor Proteins/metabolism ; Transcription Factors/genetics
    • Abstract:
      Genes from the Grainyhead-like (GRHL) family code for transcription factors necessary for the development and maintenance of various epithelia. These genes are also very important in the development of many types of cancer. However, little is known about the regulation of expression of GRHL genes. Previously, there were no systematic analyses of the promoters of GRHL genes or transcription factors that bind to these promoters. Here we report that the Krüppel-like factor 4 (KLF4) and the paired box 5 factor (PAX5) bind to the regulatory regions of the GRHL genes and regulate their expression. Ectopic expression of KLF4 or PAX5 alters the expression of GRHL genes. In KLF4-overexpressing HEK293 cells, the expression of GRHL1 and GRHL3 genes was upregulated by 32% and 60%, respectively, whereas the mRNA level of GRHL2 gene was lowered by 28% when compared to the respective controls. The levels of GRHL1 and GRHL3 expression were decreased by 30% or 33% in PAX5-overexpressing HEK293 cells. The presence of minor frequency allele of single nucleotide polymorphism rs115898376 in the promoter of the GRHL1 gene affected the binding of KLF4 to this site. The evidence presented here suggests an important role of KLF4 and PAX5 in the regulation of expression of GRHL1-3 genes.
      Competing Interests: The authors have declared that no competing interests exist.
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    • Accession Number:
      0 (DNA-Binding Proteins)
      0 (GRHL1 protein, human)
      0 (GRHL2 protein, human)
      0 (GRHL3 protein, human)
      0 (KLF4 protein, human)
      0 (Klf4 protein, mouse)
      0 (Kruppel-Like Factor 4)
      0 (Kruppel-Like Transcription Factors)
      0 (PAX5 Transcription Factor)
      0 (PAX5 protein, human)
      0 (Repressor Proteins)
      0 (Transcription Factors)
    • Publication Date:
      Date Created: 20210927 Date Completed: 20211124 Latest Revision: 20211204
    • Publication Date:
      20221213
    • Accession Number:
      PMC8476022
    • Accession Number:
      10.1371/journal.pone.0257977
    • Accession Number:
      34570823