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Nitsch, S. ; Coraor, A.E.* ; Schauer, T. ; Wu, Y.* ; Sun, J.* ; Möritz, N.* ; Funke, J.J.* ; Nagpal, H.* ; Chua, G.N.L.* ; Battistini, F.* ; Lauberth, S.M.* ; Richard, E.M.* ; Orozco, M.* ; Liu, S.* ; Desviat, L.R.* ; Fierz, B.* ; Dietz, H.* ; Roeder, R.G.* ; de Pablo, J.J.* ; Schneider, R.

H4K16 acylations destabilize chromatin architecture and facilitate transcriptional response during metabolic perturbations.

Mol. Cell 86, 24-40.e10 (2026)
DOI PMC
Creative Commons Lizenzvertrag
Open Access Green as soon as Postprint is submitted to ZB.
Histone modifications play crucial roles in genome function. However, how chromatin integrates physiological and metabolic responses at the molecular level remains largely unknown. Acetylation of histone H4 lysine 16 (H4K16ac) is unique, as it directly regulates chromatin architecture. Here, we investigated the roles of two additional H4K16 short-chain acylations, propionylation (H4K16pr) and butyrylation (H4K16bu), in chromatin architecture and transcriptional regulation. We demonstrate distinct in vitro effects of H4K16 acylations on chromatin structure, including inter- and intra-nucleosomal interactions. Utilizing a mouse model of the metabolic disease propionic acidemia, we reveal a transcriptional response concomitant with changes in H4K16 acylations in vivo. Our work suggests the importance of simultaneous action of histone acylations for transcriptional robustness through effects on nucleosomal interactions. We propose that this mode of action distinguishes H4K16 acylations from other modifications that also differ by one carbon, such as methylations.
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Publication type Article: Journal article
Document type Scientific Article
Keywords H4k16 Acylations ; Chromatin Dynamics ; Metabolic Challenge; Histone Acetyltransferase Mof; Nucleosome Core Particle; Molecular-dynamics; Internucleosome Interactions; H4-k16 Acetylation; Single-molecule; Free-energy; Dna; Protein; Acid
ISSN (print) / ISBN 1097-2765
e-ISSN 1097-4164
Journal Molecular Cell
Quellenangaben Volume: 86, Issue: 1, Pages: 24-40.e10 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Grants Fondo Europeo de Desarrollo Regional
Helmholtz Gemeinschaft
National Science Foundation
Department of Energy, Basic Energy Sciences
Division of Materials Science and Engineering, through the Midwest Integrated Center for Computational Materials (MICCoM)
National Science Foundation Graduate Research Fellowship
Blood Cancer United Specialized Center of Research
NIH/National Institute of General Medical Sciences
Swiss National Science Foundation
EPFL
European Regional Development Fund
Fundacion Ramon Areces
BioExcel-3: Centre of Excellence for Computational Biomolecular Research
Spanish Ministry of Science
Deutsche Forschungsgemeinschaft (DFG)