Improved Mass Spectrometry-Based Methods Reveal Abundant Propionylation and Tissue-Specific Histone Propionylation Profiles

Autor(es)

Vai, Alessandro ; Noberini, Roberta ; Ghirardi, Chiara ; de Paula, Dieggo Rodrigues ; Carminati, Michele ; Pallavi, Rani ; Araujo, Nathalia ; Varga-Weisz, Patrick ; Bonaldi, Tiziana

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR & CELLULAR PROTEOMICS; v. 23, n. 7, p. 14-pg., 2024-07-01.

Resumo

Histone posttranslational modifications (PTMs) have crucial roles in a multitude of cellular processes, and their aberrant levels have been linked with numerous diseases, including cancer. Although histone PTM investigations have focused so far on methylations and acetylations, alternative long-chain acylations emerged as new dimension, as they are linked to cellular metabolic states and affect gene expression through mechanisms distinct from those regulated by acetylation. Mass spectrometry is the most powerful, comprehensive, and unbiased method to study histone PTMs. However, typical mass spectrometry- based protocols for histone PTM analysis do not allow the identification of naturally occurring propionylation and butyrylation. Here, we present improved state-of-the-art sample preparation and analysis protocols to quantitate these classes of modifications. After testing different derivatization methods coupled to protease digestion, we profiled common histone PTMs and histone acylations in seven mouse tissues and human normal and tumor breast clinical samples, obtaining a map of propionylations and butyrylations found in different tissue contexts. A quantitative histone PTM analysis also revealed a contribution of histone acylations in discriminating different tissues, also upon perturbation with antibiotics, and breast cancer samples from the normal counterpart. Our results show that profiling only classical modifications is limiting and highlight the importance of using sample preparation methods that allow the analysis of the widest possible spectrum of histone modifications, paving the way for deeper insights into their functional significance in cellular processes and disease states. (AU)

• Processo FAPESP: 19/16113-5 - Remodelamento da cromatina na interação hospedeiro-microbiota em condição de saúde e doença
• Beneficiário: Patrick Daniel Varga-Weisz
• Modalidade de apoio: Auxílio à Pesquisa - Programa SPEC
• Processo FAPESP: 21/00398-0 - Interação entre a microbiota e modificações de histonas no intestino saudável
• Beneficiário: Dieggo Rodrigues de Paula
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 21/05269-4 - Identificação de mecanismos específicos de remodelamento
• Beneficiário: Nathália Vitória Pereira Araújo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 23/10157-6 - Avaliação do panorama de acilações pós-traducional de histonas causadas por ácidos graxos de cadeia curta no intestino
• Beneficiário: Dieggo Rodrigues de Paula
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto