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| Subject Categories: Chromatin & Transcription | Differentiation & Death |
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| The EMBO Journal
(2007) 26, 3616–3628, doi:10.1038/sj.emboj.7601789 Published online 12 July 2007 |
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HP1 guides neuronal fate by timing E2F-targeted genes silencing during terminal differentiation |
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| Irina Panteleeva1, 2, 6, Stéphanie Boutillier1, 2, 6, Violaine See3, Dave G Spiller3, Caroline Rouaux1, 2, Geneviève Almouzni4, Delphine Bailly4, Christèle Maison4, Helen C Lai5, Jean-Philippe Loeffler1, 2 and Anne-Laurence Boutillier1, 2 |
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1 INSERM, U692, Laboratoire de Signalisations Moléculaires et Neurodégénérescence, Strasbourg, France 2 Université Louis Pasteur, Faculté de médecine, UMRS692, Strasbourg, France 3 Centre for Cell Imaging, University of Liverpool, Liverpool L69 7ZB, UK 4 UMR 218 CNRS, Institut Curie, Paris France 5 Department of Neuroscience, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas To whom correspondence should be addressed Anne-Laurence Boutillier, INSERM, U692, Laboratoire de Signalisations Moléculaires et Neurodégénérescence, Faculté de médecine, 11 rue Humann, Strasbourg 67085, France. Tel.: +33 390 24 30 82; Fax: +33 390 24 30 65; E-mail: laurette@neurochem.u-strasbg.fr Jean-Philippe Loeffler, INSERM, U692, Laboratoire de Signalisations Moléculaires et Neurodégénérescence, Faculté de médecine, 11 rue Humann, Strasbourg 67085, France. Tel.: +33 390 24 30 82; Fax: +33 390 24 30 65; E-mail: loeffler@neurochem.u-strasbg.fr 6 These authors contributed equally to this work. Received 21 November 2006; Accepted 11 June 2007; Published online 12 July 2007. |
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| Abstract |
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A critical step of neuronal terminal differentiation is the permanent withdrawal from the cell cycle that requires the silencing of genes that drive mitosis. Here, we describe that the isoform of the heterochromatin protein 1 (HP1) protein family exerts such silencing on several E2F-targeted genes. Among the different isoforms, HP1 levels progressively increase throughout differentiation and take over HP1 binding on E2F sites in mature neurons. When overexpressed, only HP1 is able to ensure a timed repression of E2F genes. Specific inhibition of HP1 expression drives neuronal progenitors either towards death or cell cycle progression, yet preventing the expression of the neuronal marker microtubule-associated protein 2. Furthermore, we provide evidence that this mechanism occurs in cerebellar granule neurons in vivo, during the postnatal development of the cerebellum. Finally, our results suggest that E2F-targeted genes are packaged into higher-order chromatin structures in mature neurons relative to neuroblasts, likely reflecting a transition from a 'repressed' versus 'silenced' status of these genes. Together, these data present new epigenetic regulations orchestrated by HP1 isoforms, critical for permanent cell cycle exit during neuronal differentiation. |
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| Keywords: E2F, heterochromatin, HP1, neuronal terminal differentiation, transcription |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHHP1α guides neuronal fate by timing E2F-targeted genes silencing during terminal differentiation The EMBO Journal Article Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration The EMBO Journal Article (15 Dec 2003) Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration The EMBO Journal Article (15 Dec 2003) |
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