Use of histones deacetylases inhibitors in bovine somatic cell nuclear transfer.

• Grant number: 13/06673-7
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): July 01, 2013
• Effective date (End): June 30, 2016
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Flávio Vieira Meirelles
• Grantee: Juliano Rodrigues Sangalli
• Home Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Associated scholarship(s): 14/21097-5 - Dietary effects on the sperm epigenome, BE.EP.DR

Abstract

Since the SCNT was demonstrated to be possible in mammals, progress have been made, but the widespread use of cloning is hampered by low efficiency. Among the factors affecting SCNT efficiency, aberrant imprinted gene expression and chromatin compaction restricting nuclear reprogramming are thought to be the main causes. The histone deacetylases inhibitors arose as a powerful tool to elucidate the mechanisms underlying nuclear reprogramming and improve production of cloned animals, but its effects are not fully understood. For this reason the aim of this work is to investigate the effects of two histone deacetylases inhibitors, Valproic Acid and B-Hydroxybutyric Acid on the cell epigenome and metabolism. The objective of these treatments is to increase the global levels of histone acetylation in nuclear donors cells, turning them more amenable to be reprogrammed by oocytes and improve bovine SCNT efficiency. Also, this project proposes the creation of an in vitro model to study how environmental/nutritional factors or chromatin-modifying agents modify the cellular epigenome and if these epigenetic modifications are altered after nuclear reprogramming, or if they are transmitted to daughter-cells. The investigation of the effects of histone deacetylases inhibition on nuclear donors cells epigenome and metabolism will help to answer questions of basic and applied sciences to animal reproduction. Furthermore, the comprehension of these mechanisms will help the appearance of new therapeutic approaches, as well the use of natural or synthetic molecules, aiming to target activity of chromatin-modifying enzymes to heal diseases.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANGALLI, JULIANO RODRIGUES; SAMPAIO, RAFAEL VILAR; DEL COLLADO, MAITE; DA SILVEIRA, JULIANO COELHO; CAMARA DE BEM, TIAGO HENRIQUE; PERECIN, FELIPE; SMITH, LAWRENCE CHARLES; MEIRELLES, FLAVIO VIEIRA. Metabolic gene expression and epigenetic effects of the ketone body beta-hydroxybutyrate. SCIENTIFIC REPORTS, v. 8, SEP 13 2018. Web of Science Citations: 2.

SANGALLI, JULIANO RODRIGUES; CHIARATTI, MARCOS ROBERTO; CAMARA DE BEM, TIAGO HENRIQUE; DE ARAUJO, RENO ROLDI; BRESSAN, FABIANA FERNANDES; SAMPAIO, RAFAEL VILAR; PERECIN, FELIPE; SMITH, LAWRENCE CHARLES; KING, WILLIAN ALLAN; MEIRELLES, FLAVIO VIEIRA. Development to Term of Cloned Cattle Derived from Donor Cells Treated with Valproic Acid. PLoS One, v. 9, n. 6 JUN 24 2014. Web of Science Citations: 26.