Center for Research on Infectious Diseases, Instituto Nacional de Salud Pública, Cuernavaca 62100, Mexico.
Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Int J Mol Sci. 2023 Feb 20;24(4):4212. doi: 10.3390/ijms24044212.
The human 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 and 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 . 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.
该人类基因编码一个 AT 钩转录因子，其表达参与各种细胞过程。本研究的目的是鉴定参与 T 细胞激活的基因中潜在的 AKNA 结合位点，并验证选定的基因。在这里，我们分析了 ChIP-seq 和微阵列分析，以确定 AKNA 在 T 细胞淋巴细胞中结合的基序和改变的细胞过程。此外，我们通过 RT-qPCR 进行了验证分析，以评估 AKNA 在促进和表达中的作用。我们发现了五个可能作为 AKNA 反应元件的富含 AT 的基序。我们在激活的 T 细胞中的超过一千个基因的启动子区域中鉴定出这些富含 AT 的基序，并证明 AKNA 诱导参与辅助 T 细胞激活的基因的表达，如。基因组富集和富含 AT 的基序分析预测表明，AKNA 是一种转录因子，可以通过识别参与不同分子途径和过程的众多基因中的富含 AT 的基序，潜在地调节基因表达。在富含 AT 的基因激活的细胞过程中，我们发现了潜在受 AKNA 调节的炎症途径，表明 AKNA 在 T 细胞激活过程中充当主调控因子。
