Critical Role of the Transcription Factor AKNA in T-Cell Activation: An Integrative Bioinformatics Approach.
Abrahan Ramírez-GonzálezPedro Antonio Ávila-LópezMargarita Bahena-RománCarla O Contreras-OchoaAlfredo Lagunas MartínezElizabeth LangleyJoaquín Manzo-MerinoVicente Madrid-MarinaKirvis Torres-PovedaPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- transcription factor
- genome wide identification
- genome wide
- gene expression
- poor prognosis
- dna methylation
- bioinformatics analysis
- binding protein
- copy number
- endothelial cells
- risk assessment
- high throughput
- dendritic cells
- regulatory t cells
- oxidative stress
- single cell
- circulating tumor cells
- induced pluripotent stem cells