Critical Role of the Transcription Factor AKNA in T-Cell Activation: An Integrative Bioinformatics Approach

Int J Mol Sci. 2023 Feb 20;24(4):4212. doi: 10.3390/ijms24044212.

Abstract

The human akna gene encodes an AT-hook transcription factor, the expression of which is involved in various cellular processes. The goal of this study was to identify potential AKNA binding sites in genes that participate in T-cell activation and validate selected genes. Here we analyzed ChIP-seq and microarray assays to determine AKNA-binding motifs and the cellular process altered by AKNA in T-cell lymphocytes. In addition, we performed a validation analysis by RT-qPCR to assess AKNA's role in promoting IL-2 and CD80 expression. We found five AT-rich motifs that are potential candidates as AKNA response elements. We identified these AT-rich motifs in promoter regions of more than a thousand genes in activated T-cells, and demonstrated that AKNA induces the expression of genes involved in helper T-cell activation, such as IL-2. The genomic enrichment and prediction of AT-rich motif analyses demonstrated that AKNA is a transcription factor that can potentially modulate gene expression by recognizing AT-rich motifs in a plethora of genes that are involved in different molecular pathways and processes. Among the cellular processes activated by AT-rich genes, we found inflammatory pathways potentially regulated by AKNA, suggesting AKNA is acting as a master regulator during T-cell activation.

Keywords: AKNA; AT-hook transcription factor; cell activation; computational biology; immune response.

MeSH terms

  • Computational Biology
  • DNA-Binding Proteins* / metabolism
  • Humans
  • Interleukin-2 / metabolism
  • Nuclear Proteins / genetics
  • T-Lymphocytes / metabolism
  • Transcription Factors* / metabolism

Substances

  • Transcription Factors
  • DNA-Binding Proteins
  • Interleukin-2
  • Nuclear Proteins
  • AKNA protein, human