title: Nuclear translocation of beta-actin is involved in transcriptional regulation during macrophage differentiation of HL-60 cells.
abstract: Studies have shown that nuclear translocation of actin occurs under certain conditions of cellular stress; however, the functional significance of actin import remains unclear. Here, we demonstrate that during the phorbol 12-myristate 13-acetate (PMA)-induced differentiation of HL-60 cells toward macrophages, beta-actin translocates from the cytoplasm to the nucleus and that this process is dramatically inhibited by pretreatment with p38 mitogen-activated protein kinase inhibitors. Using chromatin immunoprecipitation-on-chip assays, the genome-wide maps of beta-actin binding to gene promoters in response to PMA treatment is analyzed in HL-60 cells. A gene ontology-based analysis shows that the identified genes belong to a broad spectrum of functional categories such as cell growth and differentiation, signal transduction, response to external stimulus, ion channel activity, and immune response. We also demonstrate a correlation between beta-actin occupancy and the recruitment of RNA polymerase II at six selected target genes, and beta-actin knockdown decreases the mRNA expression levels of these target genes induced by PMA. We further show that nuclear beta-actin is required for PMA-induced transactivation of one target gene, solute carrier family 11 member 1, which is important for macrophage activation. Our data provide novel evidence that nuclear accumulation of beta-actin is involved in transcriptional regulation during macrophage-like differentiation of HL-60 cells.
authors.affiliation: Department of Medicine and Human Genetics and Department of Biology, Bioinformatics Centre, McGill University, McGill University Health Centre, Montreal General Hospital Research Institute, Montreal, QC, Canada.
authors.forename: Yong Zhong
authors.initials: YZ
authors.lastname: Xu
authors.forename: Thusanth
authors.initials: T
authors.lastname: Thuraisingam
authors.forename: David Anderson de Lima
authors.initials: DA
authors.lastname: Morais
authors.forename: Marek
authors.initials: M
authors.lastname: Rola-Pleszczynski
authors.forename: Danuta
authors.initials: D
authors.lastname: Radzioch
mesh_terms: D000199:Actins / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D018922:HL-60 Cells; D006801:Humans; D017403:In Situ Hybridization; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D000199:Actins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013755:Tetradecanoylphorbol Acetate