Abstract
The Akirin family of transcription cofactors are involved throughout the metazoan in the regulation of different biological processes 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 this 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 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 biological processes 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.
Highlights
57 The Akirin ( known as Subolesin (SUB) in ticks) family constitute a model for the study58 of host-pathogen molecular interactions and functional biology due to their conserved59 function throughout the metazoan in the regulation of different biological processes (BPs)60 such as immunity, interdigital regression, muscle and neural development [1-10]
The results reported here demonstrated for the first time the physical Akirin2-histone H3.1 interaction, further supporting that Akirin2/SUB may be involved in chromatin remodeling for the regulation of gene expression
Complements supports the key role of this regulatory protein throughout the metazoan [1, 2, 7], which resulted in evolutionary adaptations to complement its function if required
Summary
57 The Akirin ( known as Subolesin (SUB) in ticks) family constitute a model for the study58 of host-pathogen molecular interactions and functional biology due to their conserved59 function throughout the metazoan in the regulation of different biological processes (BPs)60 such as immunity, interdigital regression, muscle and neural development [1-10]. 59 function throughout the metazoan in the regulation of different biological processes (BPs). Akirin are considered transcription cofactors without catalytic or DNA-binding capability involved in the regulation of signaling pathways such as immune deficiency (IMD), tumor necrosis. 65 Brg1/Brm-associated factor (BAF) chromatin remodeling complexes [1, 5, 11-14]. It has 66 been shown that Akirin proteins exert its regulatory function primarily through interaction. 67 with other proteins (Akirin-interacting proteins, IPs) such as transcription factors, chromatin. (Akirin2), the functional homolog of Drosophila melanogaster Akirin and tick SUB, has been shown to regulate various BPs in a biological context, cell type and stimulus-dependent. 71 manner, by acting as a link between NF-κB and chromatin remodeling complexes. 72 (remodelers) for transcriptional regulation [14, 22]
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