Beta-Actin Is Involved in Modulating Erythropoiesis during Development by Fine-Tuning Gata2 Expression Levels

Tondeleir, Davina; Drogat, Benjamin; Slowicka, Karolina; Bakkali, Karima; Bartunkova, Sonia; Goossens, Steven; Haigh, Jody J.; Ampè, Christophe

doi:10.1371/journal.pone.0067855

Cited by 18 publications

(21 citation statements)

References 43 publications

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“…In the few studies that used beta-actin ablation in mouse models, apoptosis was never studied. However, we recently demonstrated a role for beta-actin in cell homeostasis and as a transcriptional modulator of Gata2 during mouse embryogenesis [10], [12]. Nuclear functions of actin have been contested for more than 20 years but a role for actin as a transcriptional modulator is now firmly established.…”

Section: Discussionmentioning

confidence: 99%

Beta-Actin Is Required for Proper Mouse Neural Crest Ontogeny

et al. 2014

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The mouse genome consists of six functional actin genes of which the expression patterns are temporally and spatially regulated during development and in the adult organism. Deletion of beta-actin in mouse is lethal during embryonic development, although there is compensatory expression of other actin isoforms. This suggests different isoform specific functions and, more in particular, an important function for beta-actin during early mammalian development. We here report a role for beta-actin during neural crest ontogeny. Although beta-actin null neural crest cells show expression of neural crest markers, less cells delaminate and their migration arrests shortly after. These phenotypes were associated with elevated apoptosis levels in neural crest cells, whereas proliferation levels were unchanged. Specifically the pre-migratory neural crest cells displayed higher levels of apoptosis, suggesting increased apoptosis in the neural tube accounts for the decreased amount of migrating neural crest cells seen in the beta-actin null embryos. These cells additionally displayed a lack of membrane bound N-cadherin and dramatic decrease in cadherin-11 expression which was more pronounced in the pre-migratory neural crest population, potentially indicating linkage between the cadherin-11 expression and apoptosis. By inhibiting ROCK ex vivo, the knockout neural crest cells regained migratory capacity and cadherin-11 expression was upregulated. We conclude that the presence of beta-actin is vital for survival, specifically of pre-migratory neural crest cells, their proper emigration from the neural tube and their subsequent migration. Furthermore, the absence of beta-actin affects cadherin-11 and N-cadherin function, which could partly be alleviated by ROCK inhibition, situating the Rho-ROCK signaling in a feedback loop with cadherin-11.

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Section: Discussionmentioning

confidence: 99%

Beta-Actin Is Required for Proper Mouse Neural Crest Ontogeny

et al. 2014

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“…Growing evidence has indicated that nuclear actin, together with nuclear myosin-1 has a general role in transcription (15) and that nuclear actin polymerization is necessary for the expression of factors in nuclear reprogramming, possibly through a chromatin-based mechanism (16,17). Consistent with a general role in nuclear reprogramming, homozygous b-actin knockout in mice is embryonic lethal, and this phenotype seems to be associated with impaired erythropoiesis (18). There is also evidence that actin is involved in the long-range repositioning of gene loci (12,19).…”

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confidence: 99%

β‐Actin‐dependent global chromatin organization and gene expression programs control cellular identity

et al. 2018

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During differentiation and development, cell fate and identity are established by waves of genetic reprogramming. Although the mechanisms are largely unknown, during these events, dynamic chromatin reorganization is likely to ensure that multiple genes involved in the same cellular functions are coregulated, depending on the nuclear environment. In this study, using high-content screening of embryonic fibroblasts from a β-actin knockout (KO) mouse, we found major chromatin rearrangements and changes in histone modifications, such as methylated histone (H)3-lysine-(K)9. Genome-wide H3K9 trimethylation-(Me)3 landscape changes correlate with gene up- and down-regulation in β-actin KO cells. Mechanistically, we found loss of chromatin association by the Brahma-related gene ( Brg)/Brahma-associated factor (BAF) chromatin remodeling complex subunit Brg1 in the absence of β-actin. This actin-dependent chromatin reorganization was concomitant with the up-regulation of sets of genes involved in angiogenesis, cytoskeletal organization, and myofibroblast features in β-actin KO cells. Some of these genes and phenotypes were gained in a β-actin dose-dependent manner. Moreover, reintroducing a nuclear localization signal-containing β-actin in the knockout cells affected nuclear features and gene expression. Our results suggest that, by affecting the genome-wide organization of heterochromatin through the chromatin-binding activity of the BAF complex, β-actin plays an essential role in the determination of gene expression programs and cellular identity.-Xie, X., Almuzzaini, B., Drou, N., Kremb, S., Yousif, A., Östlund Farrants, A.-K., Gunsalus, K., Percipalle, P. β-Actin-dependent global chromatin organization and gene expression programs control cellular identity.

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“…However, it was demonstrated previously, that β- and γ-actin isoforms are able to fulfill different functions, e.g. in cell motility [13,22,23,31,74,75], cell division [24], gene transcription [76], endothelial cell motility and neovessel maintenance [77] as well as in developmental processes [78,79]. …”

Section: Discussionmentioning

confidence: 99%

Involvement of β- and γ-actin isoforms in actin cytoskeleton organization and migration abilities of bleb-forming human colon cancer cells

et al. 2017

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Amoeboid movement is characteristic for rounded cells, which do not form strong adhesion contacts with the ECM and use blebs as migratory protrusions. It is well known that actin is the main component of mature forms of these structures, but the exact role fulfilled by non-muscle actin isoforms β- and γ- in bleb formation and migration of these cells is still not fully understood. The aim of this study was to establish the role of β- and γ-actin in migration of bleb-forming cancer cells using isoform-specific antibodies and expression of fluorescently tagged actin isoforms. We observed, after staining with monoclonal antibodies, that both actins are present in these cells in the form of a cortical ring as well as in the area of blebs. Additionally, using simultaneous expression of differentially tagged β- and γ-actin in cells, we observed that the actin isoforms are present together in a single bleb. They were involved during bleb expansion as well as retraction. Also present in the area of these protrusions formed by both isoforms were the bleb markers–ezrin and myosin II. The overexpression of β- or γ-actin led to actin cytoskeletal rearrangement followed by the growth of migration and invasion abilities of examined human colon cancer cells, LS174T line. In summary these data prove that both actin isoforms have an impact on motility of bleb-forming cancer cells. Moreover, we conclude that monoclonal antibodies directed against actin isoforms in combination with the tagged actins are good tools to study their role in important biological processes.

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Beta-Actin Is Involved in Modulating Erythropoiesis during Development by Fine-Tuning Gata2 Expression Levels

Cited by 18 publications

References 43 publications

Beta-Actin Is Required for Proper Mouse Neural Crest Ontogeny

Beta-Actin Is Required for Proper Mouse Neural Crest Ontogeny

β‐Actin‐dependent global chromatin organization and gene expression programs control cellular identity

Involvement of β- and γ-actin isoforms in actin cytoskeleton organization and migration abilities of bleb-forming human colon cancer cells

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