The Akirin family of transcription cofactors are involved throughout the metazoan in the regulation of different biological processes (BPs) such as immunity, interdigital regression, muscle and neural development. Akirin do not have catalytic or DNA-binding capability and exert its regulatory function primarily through interacting proteins such as transcription factors, chromatin remodelers, and RNA-associated proteins. In the present study, we focused on the human Akirin2 regulome and interactome in neutrophil-like model human Caucasian promyelocytic leukemia HL60 cells. Our hypothesis is that metazoan evolved to have Akirin2 functional complements and different Akirin2-mediated mechanisms for the regulation of gene expression. To address this hypothesis, experiments were conducted using transcriptomics, proteomics and systems biology approaches in akirin2 knockdown and wildtype (WT) HL60 cells to characterize Akirin2 gene/protein targets, functional complements and to provide evidence of different mechanisms that may be involved in Akirin2-mediated regulation of gene expression. The results revealed Akirin2 gene/protein targets in multiple BPs with higher representation of immunity and identified immune response genes as candidate Akirin2 functional complements. In addition to linking chromatin remodelers with transcriptional activation, Akirin2 also interacts with histone H3.1 for regulation of gene expression.

中文翻译：

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辅助因子 Akirin2 在人类高加索中性粒细胞样 HL60 细胞模型基因表达调控中的作用。

Akirin 转录辅助因子家族在整个后生动物中参与调节不同的生物过程 (BP)，例如免疫、指间退化、肌肉和神经发育。Akirin 不具有催化或 DNA 结合能力，主要通过相互作用的蛋白质（如转录因子、染色质重塑剂和 RNA 相关蛋白）发挥其调节功能。在本研究中，我们专注于中性粒细胞样模型人高加索早幼粒细胞白血病 HL60 细胞中的人 Akirin2 调节组和相互作用组。我们的假设是后生动物进化为具有 Akirin2 功能互补物和不同的 Akirin2 介导的基因表达调控机制。为了解决这个假设，使用转录组学进行了实验，蛋白质组学和系统生物学方法在 akirin2 敲低和野生型 (WT) HL60 细胞中表征 Akirin2 基因/蛋白质靶标、功能互补物，并提供可能参与 Akirin2 介导的基因表达调控的不同机制的证据。结果揭示了多个 BPs 中的 Akirin2 基因/蛋白质靶点具有更高的免疫代表性，并将免疫反应基因确定为候选 Akirin2 功能补体。除了将染色质重塑因子与转录激活联系起来外，Akirin2 还与组蛋白 H3.1 相互作用以调节基因表达。结果揭示了多个 BPs 中的 Akirin2 基因/蛋白质靶点具有更高的免疫代表性，并将免疫反应基因确定为候选 Akirin2 功能补体。除了将染色质重塑因子与转录激活联系起来外，Akirin2 还与组蛋白 H3.1 相互作用以调节基因表达。结果揭示了多个 BPs 中的 Akirin2 基因/蛋白质靶点具有更高的免疫代表性，并将免疫反应基因确定为候选 Akirin2 功能补体。除了将染色质重塑因子与转录激活联系起来外，Akirin2 还与组蛋白 H3.1 相互作用以调节基因表达。