Dynamic Competing Histone H4 K5K8 Acetylation and Butyrylation Are Hallmarks of Highly Active Gene Promoters.
Recently discovered histone lysine acylation marks increase the functional diversity of nucleosomes well beyond acetylation. Here, we focus on histone butyrylation in the context of sperm cell differentiation. Specifically, we investigate the butyrylation of histone H4 lysine 5 and 8 at gene promoters where acetylation guides the binding of Brdt, a bromodomain-containing protein, thereby mediating stage-specific gene expression programs and post-meiotic chromatin reorganization. Genome-wide mapping data show that highly active Brdt-bound gene promoters systematically harbor competing histone acetylation and butyrylation marks at H4 K5 and H4 K8. Despite acting as a direct stimulator of transcription, histone butyrylation competes with acetylation, especially at H4 K5, to prevent Brdt binding. Additionally, H4 K5K8 butyrylation also marks retarded histone removal during late spermatogenesis. Hence, alternating H4 acetylation and butyrylation, while sustaining direct gene activation and dynamic bromodomain binding, could impact the final male epigenome features.
CNRS UMR 5309, INSERM, U1209, Université Grenoble Alpes, Institut Albert Bonniot, 38700 Grenoble, France.
Afsaneh
A
Goudarzi
Ben May Department of Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Di
D
Zhang
Ben May Department of Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
He
H
Huang
CNRS UMR 5309, INSERM, U1209, Université Grenoble Alpes, Institut Albert Bonniot, 38700 Grenoble, France.
Sophie
S
Barral
Ben May Department of Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Oh Kwang
OK
Kwon
Ben May Department of Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Shankang
S
Qi
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
Zhanyun
Z
Tang
CNRS UMR 5309, INSERM, U1209, Université Grenoble Alpes, Institut Albert Bonniot, 38700 Grenoble, France.
Thierry
T
Buchou
CNRS UMR 5309, INSERM, U1209, Université Grenoble Alpes, Institut Albert Bonniot, 38700 Grenoble, France.
Anne-Laure
AL
Vitte
Jingjie PTM Biolab (Hangzhou) Co., Ltd., Hangzhou 310018, China.
Tieming
T
He
Jingjie PTM Biolab (Hangzhou) Co., Ltd., Hangzhou 310018, China.
Zhongyi
Z
Cheng
CNRS UMR 5309, INSERM, U1209, Université Grenoble Alpes, Institut Albert Bonniot, 38700 Grenoble, France.
Emilie
E
Montellier
CNRS UMR 5309, INSERM, U1209, Université Grenoble Alpes, Institut Albert Bonniot, 38700 Grenoble, France; EMBL Grenoble, BP 181, 71 Avenue des Martyrs, 38042 Grenoble Cedex 9, France.
Jonathan
J
Gaucher
CNRS UMR 5309, INSERM, U1209, Université Grenoble Alpes, Institut Albert Bonniot, 38700 Grenoble, France.
Sandrine
S
Curtet
CNRS UMR 5309, INSERM, U1209, Université Grenoble Alpes, Institut Albert Bonniot, 38700 Grenoble, France.
Alexandra
A
Debernardi
TAGC, UMR, S 1090 INSERM Aix-Marseille Université, U928 Parc Scientifique de Luminy case 928 163, Avenue de Luminy, 13288 Marseille Cedex 9, France.
Guillaume
G
Charbonnier
TAGC, UMR, S 1090 INSERM Aix-Marseille Université, U928 Parc Scientifique de Luminy case 928 163, Avenue de Luminy, 13288 Marseille Cedex 9, France.
Denis
D
Puthier
Université Grenoble Alpes/CEA/CNRS, Institut de Biologie Structurale, 38027 Grenoble, France.
Carlo
C
Petosa
EMBL Grenoble, BP 181, 71 Avenue des Martyrs, 38042 Grenoble Cedex 9, France.
Daniel
D
Panne
CNRS UMR 5309, INSERM, U1209, Université Grenoble Alpes, Institut Albert Bonniot, 38700 Grenoble, France.
Sophie
S
Rousseaux
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
Robert G
RG
Roeder
Ben May Department of Cancer Research, The University of Chicago, Chicago, IL 60637, USA. Electronic address: yzhao2@bsd.uchicago.edu.
Yingming
Y
Zhao
CNRS UMR 5309, INSERM, U1209, Université Grenoble Alpes, Institut Albert Bonniot, 38700 Grenoble, France. Electronic address: saadi.khochbin@univ-grenoble-alpes.fr.
Saadi
S
Khochbin
D000107:Acetylation; D000818:Animals; D001665:Binding Sites; D002087:Butyrates / Q000378:metabolism*; D002454:Cell Differentiation; D042002:Chromatin Assembly and Disassembly; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D055106:Genome-Wide Association Study; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008239:Lysine; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D013090:Spermatocytes / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D000092468:Bromodomain Containing Proteins
D002087:Butyrates; D006657:Histones; D008239:Lysine; D009687:Nuclear Proteins; C518475:BRDT protein, mouse; D000092468:Bromodomain Containing Proteins