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Percipalle, PiergiorgioORCID iD iconorcid.org/0000-0002-9546-7425
Publikationer (10 of 27) Visa alla publikationer
Fukuda, N., Fukuda, T., Percipalle, P., Oda, K., Takei, N., Czaplinski, K., . . . Sasaoka, T. (2023). Axonal mRNA binding of hnRNP A/B is crucial for axon targeting and maturation of olfactory sensory neurons. Cell Reports, 42(5), Article ID 112398.
Öppna denna publikation i ny flik eller fönster >>Axonal mRNA binding of hnRNP A/B is crucial for axon targeting and maturation of olfactory sensory neurons
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2023 (Engelska)Ingår i: Cell Reports, E-ISSN 2211-1247, Vol. 42, nr 5, artikel-id 112398Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Spatiotemporal control of gene expression is important for neural development and function. Here, we show that heterogeneous nuclear ribonucleoprotein (hnRNP) A/B is highly expressed in developing olfactory sensory neurons (OSNs), and its knockout results in reduction in mature OSNs and aberrant targeting of OSN axons to the olfactory bulb. RNA immunoprecipitation analysis reveals that hnRNP A/B binds to a group of mRNAs that are highly related to axon projections and synapse assembly. Approximately 11% of the identified hnRNP A/B targets, including Pcdha and Ncam2, encode cell adhesion molecules. In Hnrnpab knockout mice, PCDHA and NCAM2 levels are significantly reduced at the axon terminals of OSNs. Furthermore, deletion of the hnRNP A/B-recognition motif in the 3′ UTR of Pcdha leads to impaired PCDHA expression at the OSN axon terminals. Therefore, we propose that hnRNP A/B facilitates OSN maturation and axon projection by regulating the local expression of its target genes at axon terminals.

Nyckelord
axonal mRNA, axon projections, cell adhesion molecules, hnRNPs, neural maturation, olfactory sensory neurons, post-transcriptional regulation, RNA binding proteins, 3′ UTR, olfactory behavior
Nationell ämneskategori
Utvecklingsbiologi Neurovetenskaper
Identifikatorer
urn:nbn:se:su:diva-220579 (URN)10.1016/j.celrep.2023.112398 (DOI)000985907600001 ()37083330 (PubMedID)2-s2.0-85152938053 (Scopus ID)
Tillgänglig från: 2023-09-01 Skapad: 2023-09-01 Senast uppdaterad: 2024-01-17Bibliografiskt granskad
Gallardo-Dodd, C. J., Oertlin, C., Record, J., Galvani, R. G., Sommerauer, C., Kuznetsov, N. V., . . . Westerberg, L. S. (2023). Exposure of volunteers to microgravity by dry immersion bed over 21 days results in gene expression changes and adaptation of T cells. Science Advances, 9(34), Article ID eadg1610.
Öppna denna publikation i ny flik eller fönster >>Exposure of volunteers to microgravity by dry immersion bed over 21 days results in gene expression changes and adaptation of T cells
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2023 (Engelska)Ingår i: Science Advances, E-ISSN 2375-2548, Vol. 9, nr 34, artikel-id eadg1610Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The next steps of deep space exploration are manned missions to Moon and Mars. For safe space missions for crew members, it is important to understand the impact of space flight on the immune system. We studied the effects of 21 days dry immersion (DI) exposure on the transcriptomes of T cells isolated from blood samples of eight healthy volunteers. Samples were collected 7 days before DI, at day 7, 14, and 21 during DI, and 7 days after DI. RNA sequencing of CD3(+) T cells revealed transcriptional alterations across all time points, with most changes occurring 14 days after DI exposure. At day 21, T cells showed evidence of adaptation with a transcriptional profile resembling that of 7 days before DI. At 7 days after DI, T cells again changed their transcriptional profile. These data suggest that T cells adapt by rewiring their transcriptomes in response to simulated weightlessness and that remodeling cues persist when reexposed to normal gravity.

Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Identifikatorer
urn:nbn:se:su:diva-221730 (URN)10.1126/sciadv.adg1610 (DOI)001054596800007 ()37624890 (PubMedID)2-s2.0-85168735207 (Scopus ID)
Tillgänglig från: 2023-09-28 Skapad: 2023-09-28 Senast uppdaterad: 2023-09-28Bibliografiskt granskad
Venit, T., Sapkota, O., Abdrabou, W. S., Loganathan, P., Pasricha, R., Mahmood, S. R., . . . Percipalle, P. (2023). Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice. Nature Communications, 14, Article ID 6328.
Öppna denna publikation i ny flik eller fönster >>Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice
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2023 (Engelska)Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 14, artikel-id 6328Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Metabolic reprogramming is one of the hallmarks of tumorigenesis. Here, we show that nuclear myosin 1 (NM1) serves as a key regulator of cellular metabolism. NM1 directly affects mitochondrial oxidative phosphorylation (OXPHOS) by regulating mitochondrial transcription factors TFAM and PGC1α, and its deletion leads to underdeveloped mitochondria inner cristae and mitochondrial redistribution within the cell. These changes are associated with reduced OXPHOS gene expression, decreased mitochondrial DNA copy number, and deregulated mitochondrial dynamics, which lead to metabolic reprogramming of NM1 KO cells from OXPHOS to aerobic glycolysis.This, in turn, is associated with a metabolomic profile typical for cancer cells, namely increased amino acid-, fatty acid-, and sugar metabolism, and increased glucose uptake, lactate production, and intracellular acidity. NM1 KO cells form solid tumors in a mouse model, suggesting that the metabolic switch towards aerobic glycolysis provides a sufficient carcinogenic signal. We suggest that NM1 plays a role as a tumor suppressor and that NM1 depletion may contribute to the Warburg effect at the onset of tumorigenesis.

Nationell ämneskategori
Cellbiologi
Identifikatorer
urn:nbn:se:su:diva-225763 (URN)10.1038/s41467-023-42093-w (DOI)001095507700033 ()37816864 (PubMedID)2-s2.0-85173687226 (Scopus ID)
Anmärkning

For correction, see: Nat Commun 14, 7878 (2023). DOI: 10.1038/s41467-023-43936-2

Tillgänglig från: 2024-01-23 Skapad: 2024-01-23 Senast uppdaterad: 2024-01-23Bibliografiskt granskad
Mahmood, S. R., El Said, N. H., Gunsalus, K. C. & Percipalle, P. (2023). β-actin mediated H3K27ac changes demonstrate the link between compartment switching and enhancer-dependent transcriptional regulation. Genome Biology, 24, Article ID 18.
Öppna denna publikation i ny flik eller fönster >>β-actin mediated H3K27ac changes demonstrate the link between compartment switching and enhancer-dependent transcriptional regulation
2023 (Engelska)Ingår i: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 24, artikel-id 18Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Recent work has demonstrated that three-dimensional genome organization is directly affected by changes in the levels of nuclear cytoskeletal proteins such as β-actin. The mechanisms which translate changes in 3D genome structure into changes in transcription, however, are not fully understood. Here, we use a comprehensive genomic analysis of cells lacking nuclear β-actin to investigate the mechanistic links between compartment organization, enhancer activity, and gene expression.

Results: Using HiC-Seq, ATAC-Seq, and RNA-Seq, we first demonstrate that transcriptional and chromatin accessibility changes observed upon β-actin loss are highly enriched in compartment-switching regions. Accessibility changes within compartment switching genes, however, are mainly observed in non-promoter regions which potentially represent distal regulatory elements. Our results also show that β-actin loss induces widespread accumulation of the enhancer-specific epigenetic mark H3K27ac. Using the ABC model of enhancer annotation, we then establish that these epigenetic changes have a direct impact on enhancer activity and underlie transcriptional changes observed upon compartment switching. A complementary analysis of fibroblasts undergoing reprogramming into pluripotent stem cells further confirms that this relationship between compartment switching and enhancer-dependent transcriptional change is not specific to β-actin knockout cells but represents a general mechanism linking compartment-level genome organization to gene expression.

Conclusions: We demonstrate that enhancer-dependent transcriptional regulation plays a crucial role in driving gene expression changes observed upon compartment-switching. Our results also reveal a novel function of nuclear β-actin in regulating enhancer function by influencing H3K27 acetylation levels.

Nyckelord
3D genome organization, Enhancer regulation, Transcriptional regulation, Nuclear actin
Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
urn:nbn:se:su:diva-215181 (URN)10.1186/s13059-023-02853-9 (DOI)000920693700001 ()36698204 (PubMedID)2-s2.0-85146821452 (Scopus ID)
Tillgänglig från: 2023-03-01 Skapad: 2023-03-01 Senast uppdaterad: 2023-03-01Bibliografiskt granskad
Hunashal, Y., Percipalle, M., Molnár, T., Kardos, J., Percipalle, P. & Esposito, G. (2022). Approaching Protein Aggregation and Structural Dynamics by Equilibrium and Nonequilibrium Paramagnetic Perturbation. Analytical Chemistry, 94(31), 10949-10958
Öppna denna publikation i ny flik eller fönster >>Approaching Protein Aggregation and Structural Dynamics by Equilibrium and Nonequilibrium Paramagnetic Perturbation
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2022 (Engelska)Ingår i: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 94, nr 31, s. 10949-10958Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

PENELOP (Paramagnetic Equilibrium vs Nonequilibrium magnetization Enhancement or LOss Perturbation) is the presented nuclear magnetic resonance (NMR) approach to identify at once the location of proteins' exposed surface, hindered accessibility, and exchange processes occurring on a mu s-ms time scale. In addition to mapping the protein surface accessibility, the application of this method under specific conditions makes it possible to distinguish conformational mobility and chemical exchange processes, thereby providing an alternative to characterization by more demanding techniques (transverse relaxation dispersion, saturation transfer, and high-pressure NMR). Moreover, its high sensitivity enables studying samples at low, physiologically more relevant concentrations. Association, dynamics, and oligomerization are addressed by PENELOP for a component of SARS-CoV-2 replication transcription complex and an amyloidogenic protein.

Nationell ämneskategori
Kemi
Identifikatorer
urn:nbn:se:su:diva-208297 (URN)10.1021/acs.analchem.2c00751 (DOI)000834107200001 ()35877130 (PubMedID)2-s2.0-85135894637 (Scopus ID)
Tillgänglig från: 2022-08-29 Skapad: 2022-08-29 Senast uppdaterad: 2022-08-29Bibliografiskt granskad
Hari-Gupta, Y., Fili, N., dos Santos, Á., Cook, A. W., Gough, R. E., Reed, H. C. W., . . . Toseland, C. P. (2022). Myosin VI regulates the spatial organisation of mammalian transcription initiation. Nature Communications, 13, Article ID 1346.
Öppna denna publikation i ny flik eller fönster >>Myosin VI regulates the spatial organisation of mammalian transcription initiation
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2022 (Engelska)Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 13, artikel-id 1346Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

During transcription, RNA Polymerase II (RNAPII) is spatially organised within the nucleus into clusters that correlate with transcription activity. While this is a hallmark of genome regulation in mammalian cells, the mechanisms concerning the assembly, organisation and stability remain unknown. Here, we have used combination of single molecule imaging and genomic approaches to explore the role of nuclear myosin VI (MVI) in the nanoscale organisation of RNAPII. We reveal that MVI in the nucleus acts as the molecular anchor that holds RNAPII in high density clusters. Perturbation of MVI leads to the disruption of RNAPII localisation, chromatin organisation and subsequently a decrease in gene expression. Overall, we uncover the fundamental role of MVI in the spatial regulation of gene expression.

Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
urn:nbn:se:su:diva-206159 (URN)10.1038/s41467-022-28962-w (DOI)000804856300009 ()35292632 (PubMedID)2-s2.0-85126546582 (Scopus ID)
Tillgänglig från: 2022-06-27 Skapad: 2022-06-27 Senast uppdaterad: 2023-03-28Bibliografiskt granskad
Venit, T., El Said, N. H., Mahmood, S. R. & Percipalle, P. (2021). A dynamic actin-dependent nucleoskeleton and cell identity. Journal of Biochemistry (Tokyo), 169(3), 243-257
Öppna denna publikation i ny flik eller fönster >>A dynamic actin-dependent nucleoskeleton and cell identity
2021 (Engelska)Ingår i: Journal of Biochemistry (Tokyo), ISSN 0021-924X, E-ISSN 1756-2651, Vol. 169, nr 3, s. 243-257Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

Actin is an essential regulator of cellular functions. In the eukaryotic cell nucleus, actin regulates chromatin as a bonafide component of chromatin remodelling complexes, it associates with nuclear RNA polymerases to regulate transcription and is involved in co-transcriptional assembly of nascent RNAs into ribonucleoprotein complexes. Actin dynamics are, therefore, emerging as a major regulatory factor affecting diverse cellular processes. Importantly, the involvement of actin dynamics in nuclear functions is redefining the concept of nucleoskeleton from a rigid scaffold to a dynamic entity that is likely linked to the three-dimensional organization of the nuclear genome. In this review, we discuss how nuclear actin, by regulating chromatin structure through phase separation may contribute to the architecture of the nuclear genome during cell differentiation and facilitate the expression of specific gene programs. We focus specifically on mitochondrial genes and how their dysregulation in the absence of actin raises important questions about the role of cytoskeletal proteins in regulating chromatin structure. The discovery of a novel pool of mitochondrial actin that serves as 'mitoskeleton' to facilitate organization of mtDNA supports a general role for actin in genome architecture and a possible function of distinct actin pools in the communication between nucleus and mitochondria.

Nyckelord
chromatin and transcription regulation, development and differentiation, genome organization and integrity, mitochondria, nuclear actin
Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
urn:nbn:se:su:diva-195442 (URN)10.1093/jb/mvaa133 (DOI)000651829700002 ()33351909 (PubMedID)
Tillgänglig från: 2021-08-18 Skapad: 2021-08-18 Senast uppdaterad: 2022-02-25Bibliografiskt granskad
Record, J., Saeed, M. B., Venit, T., Percipalle, P. & Westerberg, L. S. (2021). Journey to the Center of the Cell: Cytoplasmic and Nuclear Actin in Immune Cell Functions. Frontiers in Cell and Developmental Biology, 9, Article ID 682294.
Öppna denna publikation i ny flik eller fönster >>Journey to the Center of the Cell: Cytoplasmic and Nuclear Actin in Immune Cell Functions
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2021 (Engelska)Ingår i: Frontiers in Cell and Developmental Biology, E-ISSN 2296-634X, Vol. 9, artikel-id 682294Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

Actin cytoskeletal dynamics drive cellular shape changes, linking numerous cell functions to physiological and pathological cues. Mutations in actin regulators that are differentially expressed or enriched in immune cells cause severe human diseases known as primary immunodeficiencies underscoring the importance of efficienct actin remodeling in immune cell homeostasis. Here we discuss recent findings on how immune cells sense the mechanical properties of their environement. Moreover, while the organization and biochemical regulation of cytoplasmic actin have been extensively studied, nuclear actin reorganization is a rapidly emerging field that has only begun to be explored in immune cells. Based on the critical and multifaceted contributions of cytoplasmic actin in immune cell functionality, nuclear actin regulation is anticipated to have a large impact on our understanding of immune cell development and functionality.

Nyckelord
immune cells, actin, nucleus, mechanosensing, cytoplasm
Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
urn:nbn:se:su:diva-197431 (URN)10.3389/fcell.2021.682294 (DOI)000687589600001 ()34422807 (PubMedID)
Tillgänglig från: 2021-10-03 Skapad: 2021-10-03 Senast uppdaterad: 2022-03-10Bibliografiskt granskad
Bajusz, C., Kristó, I., Abonyi, C., Venit, T., Vedelek, V., Lukácsovich, T., . . . Vilmos, P. (2021). The nuclear activity of the actin-binding Moesin protein is necessary for gene expression in Drosophila. The FEBS Journal, 288(16), 4812-4832
Öppna denna publikation i ny flik eller fönster >>The nuclear activity of the actin-binding Moesin protein is necessary for gene expression in Drosophila
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2021 (Engelska)Ingår i: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658, Vol. 288, nr 16, s. 4812-4832Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Ezrin-Radixin-Moesin (ERM) proteins play an essential role in the cytoplasm by cross-linking actin filaments with plasma membrane proteins. Research has identified the nuclear localization of ERMs, as well as the involvement of a single Drosophila ERM protein, Moesin, in nuclear mRNA exports. However, the question of how important the nuclear activity of ERM proteins are for the life of an organism has so far not been explored. Here, we present the first attempt to reveal the in vivo relevance of nuclear localization of Moesin in Drosophila. With the help of a nuclear export signal, we decreased the amount of Moesin in the nuclei of the animals. Furthermore, we observed various developmental defects, demonstrating the importance of ERM function in the nucleus for the first time. Transcriptome analysis of the mutant flies revealed that the lack of nuclear Moesin function leads to expression changes in nearly 700 genes, among them heat-shock genes. This result together with additional findings revealed that in Drosophila the expression of protein chaperones requires the nuclear functions of Moesin.

Nyckelord
Drosophila, Moesin, nucleus, Hsp, transcription
Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
urn:nbn:se:su:diva-192170 (URN)10.1111/febs.15779 (DOI)000625818100001 ()33606336 (PubMedID)
Tillgänglig från: 2021-04-17 Skapad: 2021-04-17 Senast uppdaterad: 2022-02-25Bibliografiskt granskad
Mahmood, S. R., Xie, X., El Said, N. H., Venit, T., Gunsalus, K. C. & Percipalle, P. (2021). β-actin dependent chromatin remodeling mediates compartment level changes in 3D genome architecture. Nature Communications, 12(1), Article ID 5240.
Öppna denna publikation i ny flik eller fönster >>β-actin dependent chromatin remodeling mediates compartment level changes in 3D genome architecture
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2021 (Engelska)Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 12, nr 1, artikel-id 5240Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

β-actin is a crucial component of several chromatin remodeling complexes that control chromatin structure and accessibility. The mammalian Brahma-associated factor (BAF) is one such complex that plays essential roles in development and differentiation by regulating the chromatin state of critical genes and opposing the repressive activity of polycomb repressive complexes (PRCs). While previous work has shown that β-actin loss can lead to extensive changes in gene expression and heterochromatin organization, it is not known if changes in β-actin levels can directly influence chromatin remodeling activities of BAF and polycomb proteins. Here we conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) using ATAC-Seq, HiC-seq, RNA-Seq and ChIP-Seq of various epigenetic marks. We demonstrate that β-actin levels can induce changes in chromatin structure by affecting the complex interplay between chromatin remodelers such as BAF/BRG1 and EZH2. Our results show that changes in β-actin levels and associated chromatin remodeling activities can not only impact local chromatin accessibility but also induce reversible changes in 3D genome architecture. Our findings reveal that β-actin-dependent chromatin remodeling plays a role in shaping the chromatin landscape and influences the regulation of genes involved in development and differentiation.

Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
urn:nbn:se:su:diva-197968 (URN)10.1038/s41467-021-25596-2 (DOI)000695649500018 ()34475390 (PubMedID)
Tillgänglig från: 2021-10-21 Skapad: 2021-10-21 Senast uppdaterad: 2023-03-28Bibliografiskt granskad
Organisationer
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0002-9546-7425

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