SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo s/n, Ciudad Real 13005, Spain.
Biochemistry Section, Faculty of Science and Chemical Technologies, and Regional Centre for Biomedical Research (CRIB), University of Castilla-La Mancha, Ciudad Real 13071, Spain.
Biosci Rep. 2021 Jul 30;41(7). doi: 10.1042/BSR20211120.
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.
Akirin 家族转录共因子参与后生动物的多种生物学过程（BP）的调控，如免疫、指（趾）间蹼的退化、肌肉和神经发育。Akirin 没有催化或 DNA 结合能力，主要通过与转录因子、染色质重塑因子和 RNA 相关蛋白等相互作用蛋白发挥其调节功能。在本研究中，我们专注于人类中性粒细胞样模型人类白血球白血病 HL60 细胞中的 Akirin2 调控组和互作组。我们的假设是后生动物进化出了具有功能互补的 Akirin2 和不同的 Akirin2 介导的基因表达调控机制。为了验证这一假设，我们在 Akirin2 敲低和野生型（WT）HL60 细胞中进行了转录组学、蛋白质组学和系统生物学方法的实验，以表征 Akirin2 基因/蛋白靶标、功能互补，并提供证据表明可能涉及 Akirin2 介导的基因表达调控的不同机制。结果揭示了多个 BP 中的 Akirin2 基因/蛋白靶标，其中免疫反应的代表性更高，并确定了免疫反应基因是候选的 Akirin2 功能互补物。除了将染色质重塑因子与转录激活联系起来，Akirin2 还与组蛋白 H3.1 相互作用，以调节基因表达。
