Proteasome-dependent degradation of histone subtypes is mediated by its C-terminal domain
Garcia-Gomis, Daniel (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
López Gómez, Jordi (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Calderón, A. (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Andrés Nieto, Marta (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Ponte Marull, Immaculada (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Roque Córdova, Alicia (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2024
Resum:	Histone H1 is involved in chromatin compaction and dynamics. In human cells, the H1 complement is formed by different amounts of somatic H1 subtypes, H1. 0-H1. 5 and H1X. The amount of each variant depends on the cell type, the cell cycle phase, and the time of development and can be altered in disease. However, the mechanisms regulating H1 protein levels have not been described. We have analyzed the contribution of the proteasome to the degradation of H1 subtypes in human cells using two different inhibitors: MG132 and bortezomib. H1 subtypes accumulate upon treatment with both drugs, indicating that the proteasome is involved in the regulation of H1 protein levels. Proteasome inhibition caused a global increase in cytoplasmatic H1, with slight changes in the composition of H1 bound to chromatin and chromatin accessibility and no alterations in the nucleosome repeat length. The analysis of the proteasome degradation pathway showed that H1 degradation is ubiquitin-independent. The whole protein and its C-terminal domain can be degraded directly by the 20S proteasome in vitro. Partial depletion of PA28γ revealed that this regulatory subunit contributes to H1 degradation within the cell. Our study shows that histone H1 protein levels are under tight regulation to prevent its accumulation in the nucleus. We revealed a new regulatory mechanism for histone H1 degradation, where the C-terminal disordered domain is responsible for its targeting and degradation by the 20S proteasome, a process enhanced by the regulatory subunit PA28γ.
Ajuts:	Agencia Estatal de Investigación PID2020-112783GB-C22 Agencia Estatal de Investigación BFU2017-82805-C2-2-P
Nota:	Altres ajuts: acords transformatius de la UAB
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	20S proteasome ; Histone H1 ; Intrinsically disordered domains ; PA28 ; Phosphorylation ; Proteasome inhibitors
Publicat a:	Protein science, Vol. 33, Issue 5 (May 2024) , art. e4970, ISSN 1469-896X

DOI: 10.1002/pro.4970
PMID: 38591484

17 p, 15.1 MB

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