Human BAHD1 promotes heterochromatic gene silencing
| Autor: | Jacob S. Seeler, Jean Feunteun, Béatrice Regnault, Morwenna Leguillou, Pascale Cossart, Hélène Bierne, Christian Muchardt, To Nam Tham, Anne Dumay, Eric Batsché, Sophie Kernéis-Golsteyn |
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| Přispěvatelé: | Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulation Epigénétique, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génomes et cancer (GC (FRE2939)), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Microscopie électronique (Plate-forme), Institut Pasteur [Paris], Puces à ADN (Plate-Forme 2) (PF2), Organisation Nucléaire et Oncogenèse, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA) |
| Rok vydání: | 2009 |
| Předmět: |
Transcription
Genetic Chromosomal Proteins Non-Histone Heterochromatin [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Histones 03 medical and health sciences 0302 clinical medicine Insulin-Like Growth Factor II Humans Gene Silencing Nuclear protein Heterochromatin assembly Transcription factor BAH domain 030304 developmental biology 0303 health sciences Sp1 transcription factor Multidisciplinary Models Genetic HP1 Lysine Chromosome Mapping Nuclear Proteins Promoter Biological Sciences Molecular biology Chromatin Protein Structure Tertiary Microscopy Fluorescence 030220 oncology & carcinogenesis CpG Islands Heterochromatin protein 1 polycomb epigenetic Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2009, 106 (33), pp.13826-31. ⟨10.1073/pnas.0901259106⟩ Proceedings of the National Academy of Sciences of the United States of America, 2009, 106 (33), pp.13826-31. ⟨10.1073/pnas.0901259106⟩ |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Gene silencing via heterochromatin formation plays a major role in cell differentiation and maintenance of homeostasis. Here we report the identification and characterization of a novel heterochromatinization factor in vertebrates, bromo adjacent homology domain–containing protein 1 (BAHD1). This nuclear protein interacts with HP1, MBD1, HDAC5, and several transcription factors. Through electron and immunofluorescence microscopy studies, we show that BAHD1 overexpression directs HP1 to specific nuclear sites and promotes the formation of large heterochromatic domains, which lack acetyl histone H4 and are enriched in H3 trimethylated at lysine 27 (H3K27me3). Furthermore, ectopically expressed BAHD1 colocalizes with the heterochromatic inactive X chromosome (Xi). The BAH domain is required for BAHD1 colocalization with H3K27me3, but not with the Xi chromosome. As highlighted by whole genome microarray analysis of BAHD1 knockdown cells, BAHD1 represses several proliferation and survival genes, in particular the insulin-like growth factor II gene ( IGF2 ). When overexpressed, BAHD1 specifically binds the CpG-rich P3 promoter of IGF2 , which increases MBD1 and HDAC5 targeting at this locus. This region contains DNA-binding sequences for the transcription factor SP1, with which BAHD1 coimmunoprecipitates. Collectively, these findings provide evidence that BAHD1 acts as a silencer by recruiting at specific promoters a set of proteins that coordinate heterochromatin assembly. |
| Databáze: | OpenAIRE |
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