Metabolism-driven post-translational modifications of H3K9 in early bovine embryos

Author(s)

Ispada, Jessica ^{[1, 2]} ; da Fonseca Junior, Aldcejam Martins ^[2] ; Ramos Santos, Otavio Luiz ^[2] ; de Lima, Camila Bruna ^{[1, 3, 2]} ; dos Santos, Erika Cristina ^[2] ; da Silva, Vinicius Lourenco ^[4] ; Almeida, Fernanda Nascimento ^[5] ; Leite, Saul de Castro ^[4] ; Ross, Pablo Juan ^[6] ; Milazzotto, Marcella Pecora ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Sao Paulo - Brazil

^[2] Univ Fed ABC, Ctr Nat Sci & Humanities, Lab Embryon Metab & Epigenet, Santo Andre, SP - Brazil

^[3] Univ Laval, Fac Sci Agr & Alimentat, Dept Sci Anim, Ctr Rech Reprod Dev & Sante Intergenerat CRDSI, Quebec City, PQ - Canada

^[4] Univ Fed ABC, Ctr Engn Modeling & Appl Social Sci, Bioinformat & Hlth Informat Grp, Sao Bernardo Do Campo, SP - Brazil

^[5] Univ Fed ABC, Ctr Math Computat & Cognit, Santo Andre, SP - Brazil

^[6] Univ Calif Davis, Dept Anim Sci, Davis, CA 95616 - USA

• Document type: Journal article
• Source: Reproduction; v. 162, n. 3, p. 181-191, SEP 2021.
• Web of Science Citations: 0

Abstract

Metabolic and molecular profiles were reported as different for bovine embryos with distinct kinetics during the first cleavages. In this study, we used this same developmental model (fast vs slow) to determine if the relationship between metabolism and developmental kinetics affects the levels of acetylation or tri-methylation at histone H3 lysine 9 (H3K9ac and H3K9me3, respectively). Fast and slow developing embryos presented different levels of H3K9ac and H3K9me3 from the earliest stages of development (40 and 96 hpi) and up to the blastocyst stage. For H3K9me3, both groups of embryos presented a wave of demethylation and de novo methylation, although it was more pronounced in fast than slow embryos, resulting in blastocysts with higher levels of this mark. The H3K9ac reprogramming profile was distinct between kinetics groups. While slow embryos presented a wave of deacetylation, followed by an increase in this mark at the blastocyst stage, fast embryos reduced this mark throughout all the developmental stages studied. H3K9me3 differences corresponded to writer and eraser transcript levels, while H3K9ac patterns were explained by metabolism-related gene expression. To verify if metabolic differences could alter levels of H3K9ac, embryos were cultured with sodium-iodoacetate (IA) or dichloroacetate (DCA) to disrupt the glycolytic pathway or increase acetyl-CoA production, respectively. IA reduced H3K9ac while DCA increased H3K9ac in blastocysts. Concluding, H3K9me3 and H3K9ac patterns differ between embryos with different kinetics, the second one explained by metabolic pathways involved in acetyl-CoA production. So far, this is the first study demonstrating a relationship between metabolic differences and histone post-translational modifications in bovine embryos. (AU)

• FAPESP's process: 17/18384-0 - METABOLOEPYGENETICS: THE STUDY OF THE BOVINE EMBRYO DEVELOPMENT UNDER A NEW PERSPECTIVE
• Grantee: Marcella Pecora Milazzotto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/11668-6 - Metaboloepigenetics: Interrelationships between energetic metabolism and DNA methylation in bovine embryos
• Grantee: Jéssica Ispada
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/03381-0 - CELLULAR STRESS AND ITS RELATION WITH THE KINECTICS OF IN VITRO PRODUCED BOVINE EMBRYOS
• Grantee: Marcella Pecora Milazzotto
• Support Opportunities: Regular Research Grants