Insulators recruit histone methyltransferase dMes4 to regulate chromatin of flanking genes

Autor: Olivier Bouchez, Sophie Queille, Pauline Morillon, Eldon Emberly, Adrien Gamot, Magali Hennion, Gaël Micas, Priscillia Lhoumaud, Serge Urbach, Jun Liang, Suresh Cuddapah, Dany Severac, Olivier Cuvier, Keji Zhao
Přispěvatelé: Laboratoire de biologie moléculaire eucaryote (LBME), Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA, Partenaires INRAE, Inst Genom Fonct, Mass Spectrometry Facil, Montpellier, France, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Simon Fraser Univ, Dept Phys, Burnaby, BC V5A 1S6, Canada
Jazyk: angličtina
Rok vydání: 2014
Předmět:
PROTEIN-BINDING SITES
RNA splicing
[SDV]Life Sciences [q-bio]
Histones
0302 clinical medicine
Drosophila Proteins
Histone code
TRANSCRIPTION
Genetics
Principal Component Analysis
0303 health sciences
Reverse Transcriptase Polymerase Chain Reaction
General Neuroscience
METHYLATION
Articles
Chromatin
Nucleosomes
Cell biology
DNA-Binding Proteins
Drosophila melanogaster
Histone
Histone methyltransferase
Insulator Elements
RNA Interference
DROSOPHILA GENOME
nucleosome positioning
EXPRESSION
Chromatin Immunoprecipitation
Blotting
Western
Molecular Sequence Data
RNA-POLYMERASE-II
ORGANIZATION
Biology
Models
Biological
General Biochemistry
Genetics and Molecular Biology
BOUNDARY-ELEMENT
03 medical and health sciences
TOPOISOMERASE-II
Histone H1
Two-Hybrid System Techniques
Animals
Nucleosome
[INFO]Computer Science [cs]
Eye Proteins
chromatin barrier
Molecular Biology
030304 developmental biology
General Immunology and Microbiology
Sequence Analysis
RNA
physical borders
DNA-REPLICATION
higher-order chromatin organization
Histone-Lysine N-Methyltransferase
Microarray Analysis
Chromatosome
biology.protein
Chromatin immunoprecipitation
030217 neurology & neurosurgery
Zdroj: EMBO Journal
EMBO Journal, EMBO Press, 2014, 33 (4), pp.1599-1613. ⟨10.15252/embj.201385965⟩
ISSN: 0261-4189
1460-2075
DOI: 10.15252/embj.201385965⟩
Popis: International audience; Chromosomal domains in Drosophila are marked by the insulator-binding proteins (IBPs) dCTCF/Beaf32 and cofactors that participate in regulating long-range interactions. Chromosomal borders are further enriched in specific histone modifications, yet the role of histone modifiers and nucleosome dynamics in this context remains largely unknown. Here, we show that IBP depletion impairs nucleosome dynamics specifically at the promoters and coding sequence of genes flanked by IBP binding sites. Biochemical purification identifies the H3K36 histone methyltransferase NSD/dMes-4 as a novel IBP cofactor, which specifically co-regulates the chromatin accessibility of hundreds of genes flanked by dCTCF/Beaf32. NSD/dMes-4 presets chromatin before the recruitment of transcriptional activators including DREF that triggers Set2/Hypb-dependent H3K36 trimethylation, nucleosome positioning, and RNA splicing. Our results unveil a model for how IBPs regulate nucleosome dynamics and gene expression through NSD/dMes-4, which may regulate H3K27me3 spreading. Our data uncover how IBPs dynamically regulate chromatin organization depending on distinct cofactors.
Databáze: OpenAIRE
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