References of "Close, Pierre"
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See detailMicroRNA Targeting of CoREST controls polarization of migrating cortical neurons
Volvert; Prévot, Pierre-Paul; Close, Pierre ULg et al

in Cell Reports (2014), 7(4), 1168-83

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See detailp27(Kip1) as a master regulator of cortical neuron migration.
Godin, Juliette ULg; Thomas, Noémie; Laguesse, Sophie ULg et al

Conference (2013, June)

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See detailp27(Kip1) as a master regulator of cortical neuron migration.
Godin, Juliette ULg; Thomas, Noémie; Laguesse, Sophie ULg et al

Poster (2013)

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See detailDERP6 (ELP5) and C3ORF75 (ELP6) regulate tumorigenicity and migration of melanoma cells as subunits of Elongator
Close, Pierre ULg; Gillard, Magali; Ladang, Aurélie ULg et al

in Journal of Biological Chemistry (2012)

The Elongator complex is composed of 6 subunits (Elp1-Elp6) and promotes RNAPII transcript elongation through histone acetylation in the nucleus as well as tRNA modification in the cytoplasm. This ... [more ▼]

The Elongator complex is composed of 6 subunits (Elp1-Elp6) and promotes RNAPII transcript elongation through histone acetylation in the nucleus as well as tRNA modification in the cytoplasm. This acetyltransferase complex directly or indirectly regulates numerous biological processes ranging from exocytosis and resistance to heat shock in yeast to cell migration and neuronal differentiation in higher eukaryotes. The identity of human ELP1 through ELP4 has been reported but human ELP5 and ELP6 have remained uncharacterized. Here, we report that DERP6 (ELP5) and C3ORF75 (ELP6) encode these subunits of human Elongator. We further investigated the importance and function of these two subunits by a combination of biochemical analysis and cellular assays. Our results show that DERP6/ELP5 is required for the integrity of Elongator and directly connects ELP3 to ELP4. Importantly, the migration and tumorigenicity of melanomaderived cells are significantly decreased upon Elongator depletion through ELP1 or ELP3. Strikingly, DERP6/ELP5 and C3ORF75/ELP6-depleted melanoma cells have similar defects, further supporting the idea that DERP6/ELP5 and C3ORF75/ELP6 are essential for Elongator function. Together, our data identify DERP6/ELP5 and C3ORF75/ELP6 as key players for migration, invasion and tumorigenicity of melanoma cells, as integral subunits of Elongator. [less ▲]

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See detailDBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation
Close, Pierre ULg; East, Phil; Svejstrup, Barbara et al

in Nature (2012)

Alternative messenger RNA splicing is the main reason that vast mammalian proteomic complexity can be achieved with a limited number of genes. Splicing is physically and functionally coupled to ... [more ▼]

Alternative messenger RNA splicing is the main reason that vast mammalian proteomic complexity can be achieved with a limited number of genes. Splicing is physically and functionally coupled to transcription, and is greatly affected by the rate of transcript elongation1–3. As the nascent pre-mRNA emerges from transcribing RNA polymerase II (RNAPII), it is assembled into a messenger ribonucleoprotein (mRNP) particle; this is the functional form of the nascent pre-mRNA and determines the fate of the mature transcript4. However, factors that connect the transcribing polymerase with the mRNP particle and help to integrate transcript elongation with mRNA splicing remain unclear. Here we characterize the human interactome of chromatin-associated mRNP particles. This led us to identify deleted in breast cancer 1 (DBC1) and ZNF326 (which we call ZNF-protein interacting with nuclear mRNPs and DBC1 (ZIRD)) as subunits of a novel protein complex—named DBIRD—that binds directly to RNAPII. DBIRD regulates alternative splicing of a large set of exons embedded in (A 1 T)-rich DNA, and is present at the affected exons. RNAinterference- mediated DBIRD depletion results in region-specific decreases in transcript elongation, particularly across areas encompassing affected exons. Together, these data indicate that the DBIRD complex acts at the interface between mRNP particles and RNAPII, integrating transcript elongation with the regulation of alternative splicing. [less ▲]

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See detailp27(Kip1) as a master regulator of cortical neuron migration.
Godin, Juliette ULg; Thomas, Noémie; Laguesse, Sophie ULg et al

Poster (2012)

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See detailp27(Kip1) as a master regulator of cortical neuron migration.
Godin, Juliette ULg; Thomas, Noémie; Laguesse, Sophie ULg et al

Poster (2012)

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See detailp27(Kip1) Is a Microtubule-Associated Protein that Promotes Microtubule Polymerization during Neuron Migration.
Godin, Juliette ULg; Thomas, Noemie; Laguesse, Sophie ULg et al

in Developmental Cell (2012), 23(4), 729-44

The migration of cortical interneurons is characterized by extensive morphological changes that result from successive cycles of nucleokinesis and neurite branching. Their molecular bases remain elusive ... [more ▼]

The migration of cortical interneurons is characterized by extensive morphological changes that result from successive cycles of nucleokinesis and neurite branching. Their molecular bases remain elusive, and the present work describes how p27(Kip1) controls cell-cycle-unrelated signaling pathways to regulate these morphological remodelings. Live imaging reveals that interneurons lacking p27(Kip1) show delayed tangential migration resulting from defects in both nucleokinesis and dynamic branching of the leading process. At the molecular level, p27(Kip1) is a microtubule-associated protein that promotes polymerization of microtubules in extending neurites, thereby contributing to tangential migration. Furthermore, we show that p27(Kip1) controls actomyosin contractions that drive both forward translocation of the nucleus and growth cone splitting. Thus, p27(Kip1) cell-autonomously controls nucleokinesis and neurite branching by regulating both actin and microtubule cytoskeletons. [less ▲]

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See detailp27(Kip1) as a master regulator of cortical neuron migration
Godin, Juliette ULg; Thomas, Noémie; Laguesse, Sophie ULg et al

Scientific conference (2011, June)

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See detailInvolvement of placental growth factor in Wallerian degeneration
Chaballe, Linda ULg; Close, Pierre ULg; SEMPELS, Maxime ULg et al

in Glia (2011), 59(3), 379-396

Wallerian degeneration (WD) is an inflammatory process of nerve degeneration, which occurs more rapidly in the peripheral nervous system compared with the central nervous system, resulting, respectively ... [more ▼]

Wallerian degeneration (WD) is an inflammatory process of nerve degeneration, which occurs more rapidly in the peripheral nervous system compared with the central nervous system, resulting, respectively in successful and aborted axon regeneration. In the peripheral nervous system, Schwann cells (SCs) and macrophages, under the control of a network of cytokines and chemokines, represent the main cell types involved in this process. Within this network, the role of placental growth factor (PlGF) remains totally unknown. However, properties like monocyte activation/attraction, ability to increase expression of pro-inflammatory molecules, as well as neuroprotective effects, make it a candidate likely implicated in this process. Also, nothing is described about the expression and localization of this molecule in the peripheral nervous system. To address these original questions, we decided to study PlGF expression under physiological and degenerative conditions and to explore its role in WD, using a model of sciatic nerve transection in wild-type and Pgf(-/-) mice. Our data show dynamic changes of PlGF expression, from periaxonal in normal nerve to SCs 24h postinjury, in parallel with a p65/NF-κB recruitment on Pgf promoter. After injury, SC proliferation is reduced by 30% in absence of PlGF. Macrophage invasion is significantly delayed in Pgf(-/-) mice compared with wild-type mice, which results in worse functional recovery. MCP-1 and proMMP-9 exhibit a 3-fold reduction of their relative expressions in Pgf(-/-) injured nerves, as demonstrated by cytokine array. In conclusion, this work originally describes PlGF as a novel member of the cytokine network of WD. [less ▲]

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See detailStudying RNA-Protein Interactions In Vivo By RNA Immunoprecipitation
Selth, L. A.; Close, Pierre ULg; Svejstrup, J. Q.

in Methods in Molecular Biology (Clifton, N.J.) (2011), 791

The crucial roles played by RNA-binding proteins in all aspects of RNA metabolism, particularly in the regulation of transcription, have become increasingly evident. Moreover, other factors that do not ... [more ▼]

The crucial roles played by RNA-binding proteins in all aspects of RNA metabolism, particularly in the regulation of transcription, have become increasingly evident. Moreover, other factors that do not directly interact with RNA molecules can nevertheless function proximally to RNA polymerases and have significant effects on gene expression. RNA immunoprecipitation (RIP) is a powerful technique used to detect direct and indirect interactions between individual proteins and specific RNA molecules in vivo. Here, we describe RIP methods for both yeast and mammalian cells. [less ▲]

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See detailInvolvement of Placental growth factor in Wallerian degeneration
Chaballe, Linda ULg; Close, Pierre ULg; Sempels, Maxime ULg et al

Poster (2010, September)

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See detailThe repressing function of the oncoprotein BCL-3 requires CtBP while its polyubiquitination and degradation involve the E3 ligase TBLR1
Keutgens, Aurore ULg; Shostak, Kateryna ULg; Close, Pierre ULg et al

in Molecular & Cellular Biology (2010), 30

The nuclear and oncogenic BCL-3 protein activates or represses gene transcription when bound to NF-kB proteins p50 and p52, yet the molecules that specifically interact with BCL-3 and drive BCL-3-mediated ... [more ▼]

The nuclear and oncogenic BCL-3 protein activates or represses gene transcription when bound to NF-kB proteins p50 and p52, yet the molecules that specifically interact with BCL-3 and drive BCL-3-mediated effects on gene expression remain largely uncharacterized. Moreover, GSK3-mediated phosphorylation of BCL-3 triggers its degradation through the proteasome, but the proteins involved in this degradative pathway are poorly characterized. Biochemical purification of interacting partners of BCL-3 led to the identification of CtBP as a molecule required for the ability of BCL-3 to repress gene transcription. CtBP is also required for the oncogenic potential of BCL-3 and for its ability to inhibit UV-mediated cell apoptosis in keratinocytes. We also defined the E3 ligase TBLR1 as a protein involved in BCL-3 degradation through a GSK3-independent pathway. Thus, our data demonstrate that the LSD1/CtBP complex is required for the repressing abilities of an oncogenic IkB protein, and they establish a functional link between the E3 ligase TBLR1 and NF-kB. [less ▲]

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See detailThe emerging role of lysine acetylation of non-nuclear proteins
Close, Pierre ULg; Creppe, Catherine; Gillard, Magali ULg et al

in Cellular and Molecular Life Sciences : CMLS (2010), 67(8), 1255-1264

Lysine acetylation is a post-translational modification that critically regulates gene transcription by targeting histones as well as a variety of transcription factors in the nucleus. More recent reports ... [more ▼]

Lysine acetylation is a post-translational modification that critically regulates gene transcription by targeting histones as well as a variety of transcription factors in the nucleus. More recent reports have also demonstrated that numerous proteins located outside the nucleus are also acetylated and that this modification has profound consequences on their functions. This review describes the latest findings on the substrates acetylated outside the nucleus and on the acetylases and deacetylates that catalyse these modifications. Protein acetylation is emerging as a major mechanism by which key proteins are regulated in many physiological processes such as migration, metabolism and aging as well as in pathological circumstances such as cancer and neurodegenerative disorders. [less ▲]

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See detailElongator orchestrates cerebral cortical neurogenesis
creppe, catherine; malinouskaya, lina; Volvert, Marie-Laure ULg et al

in Medecine Sciences : M/S (2010)

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See detailElongator controls the migration and differentiation of cortical neurons through acetylation of a tubulin
Creppe, Catherine ULg; Malinouskaya, Lina ULg; Volvert, Marie-Laure ULg et al

in Cell (2009), 136

The generation of cortical projection neurons relies on the coordination of radial migration with branching. Here we report that the multi-subunit histone acetyltransferase Elongator complex, which ... [more ▼]

The generation of cortical projection neurons relies on the coordination of radial migration with branching. Here we report that the multi-subunit histone acetyltransferase Elongator complex, which contributes to transcript elongation, also regulates the maturation of projection neurons. Indeed, silencing of its scaffold (Elp1) or catalytic subunit (Elp3) cell-autonomously delays the migration and impairs the branching of projection neurons. Strikingly, neurons defective in Elongator show reduced levels of acetylated alpha tubulin. A direct reduction of alpha tubulin acetylation leads to comparable defects in cortical neurons and suggests that alpha tubulin is a target of Elp3. This is further supported by the demonstration that Elp3 promotes acetylation and counteracts HDAC6-mediated deacetylation of this substrate in vitro. Our results uncover alpha tubulin as a target of the Elongator complex and suggest that a tight regulation of its acetylation underlies the maturation of cortical projection neurons. [less ▲]

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