Nuclear Translocation of β-Actin Is Involved in Transcriptional Regulation during Macrophage Differentiation of HL-60 Cells

Xu, Yong; Thuraisingam, Thusanth; Morais, David Anderson de Lima; Rola‐Pleszczynski, Marek; Radzioch, Danuta

doi:10.1091/mbc.e09-06-0534

Cited by 68 publications

(76 citation statements)

References 48 publications

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“…Because our export FLIP experiment showed that the availability of actin monomers is limiting nuclear export rates of actin, this also suggests that increased binding of actin to nuclear structures, e.g., upon transcriptional activation, would increase the levels of nuclear actin. Accordingly, transcriptionally quiescent cells have less nuclear actin (22) and differentiating, transcriptionally active macrophages display increased actin in their nuclei (23), supporting the idea that an interesting feedback-loop may exist between nuclear actin levels and transcriptional activity of the cell. Indeed, decreased nuclear actin in Ipo9-depleted cells resulted in reduction on 5-FUrd incorporation into nascent transcripts (Fig.…”

Section: Discussionmentioning

confidence: 73%

“…It remains to be determined how global the actin-dependent transcriptional repression is or whether some genes are affected more than others. The latter seems more plausible, because the lack of nuclear actin has already been shown to regulate the specific fluctuations in gene expression required for the normal function of certain epithelial cells (22) and cellular differentiation specifically accumulates actin on certain promoters (23). In Drosophila, the DNA adenine methyltransferase identification technique has revealed that actin is found associated with a special type of euchromatin, which is linked to tissue-specific gene expression (47), further suggesting that actin may have genespecific effect on transcription.…”

Section: Discussionmentioning

confidence: 99%

“…In support of this it was recently discovered that extracellular cues induce a reduction in nuclear β-actin levels resulting in cell quiescence (22). In another example, treating HL-60 cells with phorbol 12-myristate 13-acetate, which induces their differentiation, resulted in approximately 30-fold increase in levels of nuclear actin, demonstrating a dramatic shift in the cellular actin balance (23). Also amphibian oocytes, which contain massive amounts of actin in their nuclei (24), require nuclear actin polymerization for transcriptional reprogramming (21).…”

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confidence: 86%

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Active maintenance of nuclear actin by importin 9 supports transcription

Dopie

Skarp

Rajakylä

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

228

320

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Besides its essential and well established role as a component of the cytoskeleton, actin is also present in the cell nucleus, where it has been linked to many processes that control gene expression. For example, nuclear actin regulates the activity of specific transcription factors, associates with all three RNA polymerases, and is a component of many chromatin remodelling complexes. Despite the fact that two export receptors, Crm1 and exportin 6, have been linked to nuclear export of actin, the mechanism by which actin enters the nucleus to elicit these essential functions has not been determined. It is also unclear whether actin is actively exchanged between the nucleus and the cytoplasm, and whether this connection has any functional significance for the cell. By applying a variety of live-cell imaging techniques we revealed that actin constantly shuttles in and out of the nucleus. The fast transport rates, which depend on the availability of actin monomers, suggest an active transport mechanism in both directions. Importantly, we identified importin 9 as the nuclear import factor for actin. Furthermore, our RNAi experiments showed that the active maintenance of nuclear actin levels by importin 9 is required for maximal transcriptional activity. Measurements of nuclear export rates and depletion studies also clarified that nuclear export of actin is mediated by exportin 6, and not by Crm1. These results demonstrate that cytoplasmic and nuclear actin pools are dynamically connected and identify the nuclear import and export mechanisms of actin.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 86%

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Active maintenance of nuclear actin by importin 9 supports transcription

Dopie

Skarp

Rajakylä

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

228

320

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“…A recent more systematic study using ChIP-on-chip mapped the recruitment of actin to gene promoters in response to phorbol 12-myristate 13-acetate (PMA)-induced differentiation of HL-60 cells towards macrophages. This study found that in unstimulated cells only few promoters contained actin, but upon stimulation with PMA over 800 genes, with variable functional annotations, displayed enriched binding by actin [Xu et al, 2010]. Curiously, actin has also been found on intragenic regions of at least rDNA [Ye et al, 2008], however, the functional role of actin at these sites is not obvious.…”

Section: Connecting Actin To Rna Polymerasesmentioning

confidence: 81%

Actin on DNA—An ancient and dynamic relationship

Skarp

Vartiainen

2010

Cytoskeleton

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In the cytoplasm of eukaryotic cells the coordinated assembly of actin filaments drives essential cell biological processes, such as cell migration. The discovery of prokaryotic actin homologues, as well as the appreciation of the existence of nuclear actin, have expanded the scope by which the actin family is utilized in different cell types. In bacteria, actin has been implicated in DNA movement tasks, while the connection with the RNA polymerase machinery appears to exist in both prokaryotes and eukaryotes. Within the nucleus, actin has further been shown to play a role in chromatin remodeling and RNA processing, possibly acting to link these to transcription, thereby facilitating the gene expression process. The molecular mechanism by which actin exerts these newly discovered functions is still unclear, because while polymer formation seems to be required in bacteria, these species lack conventional actin-binding proteins to regulate the process. Furthermore, although the nucleus contains a plethora of actin-regulating factors, the polymerization status of actin within this compartment still remains unclear. General theme, however, seems to be actin's ability to interact with numerous binding partners. A common feature to the novel modes of actin utilization is the connection between actin and DNA, and here we aim to review the recent literature to explore how this connection is exploited in different contexts. V C 2010 Wiley-Liss, Inc.Key Words: actin, myosin, DNA, nucleus, transcription Introduction S ince the discovery of actin, a great number of actin-binding proteins (ABPs) have been found and implicated in various cellular processes. Traditionally, the reign of actin and ABPs has been limited to the cytoplasm, where they cooperate to form helical actin filaments, which can be bundled and cross-linked to different structural ends. The coordinated assembly of these filaments then drives for example cell migration, cytokinesis and membrane dynamics [reviewed in Pollard and Borisy, 2003]. However, during the past decade, actin has been transformed from an exclusively cytoskeletal component in eukaryotic cells to a multipurpose tool that most cells use in a number of processes. Especially the discovery of a function for actin in the nucleus [reviewed in Vartiainen, 2008] and identification of prokaryotic actin homologues [van den Ent et al., 2001] has yielded surprising data, which has considerably expanded the modes by which the actin family is utilized in different functional contexts. In the nucleus, actin has been shown to be involved all the way in the gene expression process from chromatin remodeling complexes through transcription to spliceosome function and mRNA export [reviewed in Percipalle, 2009]. In addition, nuclear actin also seems to affect the expression of subsets of genes by regulating the activity of specific transcription factors [Vartiainen et al., 2007]. However, the biochemical details of most of these actin-involving processes are lacking, and the nature and mechanics of the interact...

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“…PMA is used to induce macrophage differentiation in several human monocytic cell lines. THP-1 (human monocytic leukemia cell line), HL-60 (human promyelocytic leukemia cell line) and U937 (human histiocytic lymphoma cell line) change their characters including morphology and phagocytic activity from monocyte-like rather into macrophagelike [17,21,23,25]. Human PBMC-derived monocytes were also reported to differentiate into macrophage, although morphological and functional analysis was not performed [23].…”

Section: Discussionmentioning

confidence: 99%

A Rapid and Simple Method to Obtain Canine Peripheral Blood-Derived Macrophages

et al. 2011

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ABSTRACT. Macrophages play an important role in a variety of situations, including pathogen elimination, inflammation, and tissue repair. However, these cells are not fully studied in dogs, in part, due to the difficulty of efficiently isolating and culturing them in vitro. In this study, we cultured canine peripheral blood mononuclear cells (PBMCs) with 10 ng/ml of phorbol 12-myristate-13-acetate (PMA) for 5 days to obtain macrophages. A high number of round-adherent cells were obtained without the addition of any cytokine. These cells showed active phagocytic activity and a cell surface antigen profile different from dendritic cells. Our method facilitates a high yield of macrophages in a short cultivation period compared with previous studies. This method might be a powerful tool to study macrophage functions in dogs.

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Nuclear Translocation of β-Actin Is Involved in Transcriptional Regulation during Macrophage Differentiation of HL-60 Cells

Cited by 68 publications

References 48 publications

Active maintenance of nuclear actin by importin 9 supports transcription

Active maintenance of nuclear actin by importin 9 supports transcription

Actin on DNA—An ancient and dynamic relationship

A Rapid and Simple Method to Obtain Canine Peripheral Blood-Derived Macrophages

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