Dynamic Competing Histone H4 K5K8 Acetylation and Butyrylation Are Hallmarks of Highly Active Gene Promoters.
Afsaneh Goudarzi
(1)
,
Di Zhang
(2)
,
He Huang
(3)
,
Sophie Barral
(1)
,
Oh Kwang Kwon
(4)
,
Shankang Qi
(5)
,
Zhanyun Tang
(6)
,
Thierry Buchou
(1)
,
Anne-Laure Vitte
(1)
,
Tieming He
(7)
,
Zhongyi Cheng
(8)
,
Emilie Montellier
(1)
,
Jonathan Gaucher
(1)
,
Sandrine Curtet
(1)
,
Alexandra Debernardi
(1)
,
Guillaume Charbonnier
(9)
,
Denis Puthier
(9)
,
Carlo Petosa
(10)
,
Daniel Panne
(11)
,
Sophie Rousseaux
(1)
,
Robert G Roeder
(12)
,
Yingming Zhao
(5)
,
Saadi Khochbin
(1)
1
IAB -
Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
2 UA - University of Alabama [Tuscaloosa]
3 Memorial Sloane Kettering Cancer Center [New York]
4 SNU - Seoul National University [Seoul]
5 Ben May Department for Cancer Research
6 JAX - The Jackson Laboratory [Bar Harbor]
7 Research Institute
8 jingjie PTM Biolab
9 TAGC - Technologies avancées pour le génôme et la clinique
10 IBS - UMR 5075 - Institut de biologie structurale
11 EMBL - European Molecular Biology Laboratory [Grenoble]
12 Laboratory of Biochemistry and Molecular Biology
2 UA - University of Alabama [Tuscaloosa]
3 Memorial Sloane Kettering Cancer Center [New York]
4 SNU - Seoul National University [Seoul]
5 Ben May Department for Cancer Research
6 JAX - The Jackson Laboratory [Bar Harbor]
7 Research Institute
8 jingjie PTM Biolab
9 TAGC - Technologies avancées pour le génôme et la clinique
10 IBS - UMR 5075 - Institut de biologie structurale
11 EMBL - European Molecular Biology Laboratory [Grenoble]
12 Laboratory of Biochemistry and Molecular Biology
Guillaume Charbonnier
- Function : Author
- PersonId : 770901
- ORCID : 0000-0002-4425-3849
Denis Puthier
- Function : Author
- PersonId : 15210
- IdHAL : denis-puthier
- ORCID : 0000-0002-7240-5280
- IdRef : 151528969
Carlo Petosa
- Function : Author
- PersonId : 742156
- IdHAL : carlo-petosa
- ORCID : 0000-0002-9975-1167
- IdRef : 158806298
Sophie Rousseaux
- Function : Author
- PersonId : 758736
- ORCID : 0000-0001-5246-5350
- IdRef : 080608078
Abstract
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.