TY - JOUR
T1 - Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells
AU - De Dieuleveult, Maud
AU - Yen, Kuangyu
AU - Hmitou, Isabelle
AU - Depaux, Arnaud
AU - Boussouar, Fayçal
AU - Dargham, Daria Bou
AU - Jounier, Sylvie
AU - Humbertclaude, Hélène
AU - Ribierre, Florence
AU - Baulard, Céline
AU - Farrell, Nina P.
AU - Park, Bongsoo
AU - Keime, Céline
AU - Carrière, Lucie
AU - Berlivet, Soizick
AU - Gut, Marta
AU - Gut, Ivo
AU - Werner, Michel
AU - Deleuze, Jean François
AU - Olaso, Robert
AU - Aude, Jean Christophe
AU - Chantalat, Sophie
AU - Pugh, B. Franklin
AU - Gérard, Matthieu
N1 - Funding Information:
Acknowledgements We thank J. C. Andrau, S. Ravens, L. Tora and M. de Chaldée for critical reading, J. B. Charbonnier’s team for sharing material, A. Krebs, T. Ye, I. Davidson, R. Guerois and F. Ochsenbein for discussions, and A. Martel for computational assistance. This work was supported by the CEA, and by grants from the Association pour la Recherche sur le Cancer (grant 3164), the Agence Nationale de la Recherche (ANR-05-BLAN-0396), the Fondation pour la Recherche Médicale (FRM), the National Institutes of Health (grant HG004160, to B.F.P.) and from Southern Medical University (grant B1000465, to K.Y.).
Publisher Copyright:
© 2016 Macmillan Publishers Limited. All rights reserved.
PY - 2016/2/4
Y1 - 2016/2/4
N2 - ATP-dependent chromatin remodellers allow access to DNA for transcription factors and the general transcription machinery, but whether mammalian chromatin remodellers target specific nucleosomes to regulate transcription is unclear. Here we present genome-wide remodeller-nucleosome interaction profiles for the chromatin remodellers Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind one or both full nucleosomes that flank micrococcal nuclease (MNase)-defined nucleosome-free promoter regions (NFRs), where they separate divergent transcription. Surprisingly, large CpG-rich NFRs that extend downstream of annotated transcriptional start sites are nevertheless bound by non-nucleosomal or subnucleosomal histone variants (H3.3 and H2A.Z) and marked by H3K4me3 and H3K27ac modifications. RNA polymerase II therefore navigates hundreds of base pairs of altered chromatin in the sense direction before encountering an MNase-resistant nucleosome at the 3′ end of the NFR. Transcriptome analysis after remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. Whereas at active genes individual remodellers have either positive or negative roles via altering nucleosome stability, at polycomb-enriched bivalent genes the same remodellers act in an opposite manner. These findings indicate that remodellers target specific nucleosomes at the edge of NFRs, where they regulate ES cell transcriptional programs.
AB - ATP-dependent chromatin remodellers allow access to DNA for transcription factors and the general transcription machinery, but whether mammalian chromatin remodellers target specific nucleosomes to regulate transcription is unclear. Here we present genome-wide remodeller-nucleosome interaction profiles for the chromatin remodellers Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind one or both full nucleosomes that flank micrococcal nuclease (MNase)-defined nucleosome-free promoter regions (NFRs), where they separate divergent transcription. Surprisingly, large CpG-rich NFRs that extend downstream of annotated transcriptional start sites are nevertheless bound by non-nucleosomal or subnucleosomal histone variants (H3.3 and H2A.Z) and marked by H3K4me3 and H3K27ac modifications. RNA polymerase II therefore navigates hundreds of base pairs of altered chromatin in the sense direction before encountering an MNase-resistant nucleosome at the 3′ end of the NFR. Transcriptome analysis after remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. Whereas at active genes individual remodellers have either positive or negative roles via altering nucleosome stability, at polycomb-enriched bivalent genes the same remodellers act in an opposite manner. These findings indicate that remodellers target specific nucleosomes at the edge of NFRs, where they regulate ES cell transcriptional programs.
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U2 - 10.1038/nature16505
DO - 10.1038/nature16505
M3 - Article
C2 - 26814966
AN - SCOPUS:84957554030
VL - 530
SP - 113
EP - 116
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7588
ER -