دورية أكاديمية
HDAC1 and PRC2 mediate combinatorial control in SPI1/PU.1-dependent gene repression in murine erythroleukaemia
| العنوان: | HDAC1 and PRC2 mediate combinatorial control in SPI1/PU.1-dependent gene repression in murine erythroleukaemia |
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| المؤلفون: | Gregoricchio, Sebastian, Polit, Lélia, Esposito, Michela, Berthelet, Jérémy, Delestré, Laure, Evanno, Emilie, Diop, M’boyba, Gallais, Isabelle, Aleth, Hanna, Poplineau, Mathilde, Zwart, Wilbert, Rosenbauer, Frank, Rodrigues-Lima, Fernando, Duprez, Estelle, Boeva, Valentina, Guillouf, Christel |
| المساهمون: | Dynamique moléculaire de la transformation hématopoïétique (Dynamo), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Unité de génétique et biologie des cancers (U830), Institut Curie Paris -Institut National de la Santé et de la Recherche Médicale (INSERM), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC), Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes (IPC), Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Department of Computer Science ETH Zürich (D-INFK), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology Zürich (ETH Zürich), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-11-LABX-0071,WHO AM I,Determinants de l'Identité : de la molécule à l'individu(2011) |
| المصدر: | ISSN: 0305-1048. |
| بيانات النشر: | HAL CCSD Oxford University Press |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Gene Regulation, Chromatin and Epigenetics, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.CAN]Life Sciences [q-bio]/Cancer |
| الوصف: | International audience ; Although originally described as transcriptional activator, SPI1/PU.1, a major player in haematopoiesis whose alterations are associated with haematological malignancies, has the ability to repress transcription. Here, we investigated the mechanisms underlying gene repression in the erythroid lineage, in which SPI1 exerts an oncogenic function by blocking differentiation. We show that SPI1 represses genes by binding active enhancers that are located in intergenic or gene body regions. HDAC1 acts as a cooperative mediator of SPI1-induced transcriptional repression by deacetylating SPI1-bound enhancers in a subset of genes, including those involved in erythroid differentiation. Enhancer deacetylation impacts on promoter acetylation, chromatin accessibility and RNA pol II occupancy. In addition to the activities of HDAC1, polycomb repressive complex 2 (PRC2) reinforces gene repression by depositing H3K27me3 at promoter sequences when SPI1 is located at enhancer sequences. Moreover, our study identified a synergistic relationship between PRC2 and HDAC1 complexes in mediating the transcriptional repression activity of SPI1, ultimately inducing synergistic adverse effects on leukaemic cell survival. Our results highlight the importance of the mechanism underlying transcriptional repression in leukemic cells, involving complex functional connections between SPI1 and the epigenetic regulators PRC2 and HDAC1. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35871293; hal-03821715; https://hal.science/hal-03821715Test; https://hal.science/hal-03821715/documentTest; https://hal.science/hal-03821715/file/gkac613.pdfTest; PUBMED: 35871293; PUBMEDCENTRAL: PMC9371914 |
| DOI: | 10.1093/nar/gkac613 |
| الإتاحة: | https://doi.org/10.1093/nar/gkac613Test https://hal.science/hal-03821715Test https://hal.science/hal-03821715/documentTest https://hal.science/hal-03821715/file/gkac613.pdfTest |
| حقوق: | http://creativecommons.org/licenses/by-ncTest/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.3F09862D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/nar/gkac613 |
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