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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Catalytic inhibition of H3K9me2 writers disturbs epigenetic marks during bovine nuclear reprogramming

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Author(s):
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Sampaio, Rafael Vilar [1, 2, 3] ; Sangalli, Juliano Rodrigues [1, 2] ; Camara De Bem, Tiago Henrique [1] ; Ambrizi, Dewison Ricardo [1] ; del Collado, Maite [1] ; Bridi, Alessandra [1] ; Cavalcante Mendes de Avila, Ana Clara Faquineli [1] ; Macabelli, Carolina Habermann [4] ; Oliveira, Lilian de Jesus [1] ; da Silveira, Juliano Coelho [1] ; Chiaratti, Marcos Roberto [4] ; Perecin, Felipe [1] ; Bressan, Fabiana Fernandes [1] ; Smith, Lawrence Charles [3] ; Ross, Pablo J. [2] ; Meirelles, Flavio Vieira [1]
Total Authors: 16
Affiliation:
[1] Univ Sao Paulo, Fac Zootecnia & Engn Alimentos, Dept Med Vet, Pirassununga, SP - Brazil
[2] Univ Calif Davis, Dept Anim Sci, Davis, CA 95616 - USA
[3] Univ Montreal, Fac Vet Med, Ctr Rech Reprod & Fertilite, St Hyacinthe, PQ - Canada
[4] Univ Fed Sao Carlos, Dept Genet & Evolucao, Sao Carlos, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 10, n. 1 JUL 13 2020.
Web of Science Citations: 0
Abstract

Orchestrated events, including extensive changes in epigenetic marks, allow a somatic nucleus to become totipotent after transfer into an oocyte, a process termed nuclear reprogramming. Recently, several strategies have been applied in order to improve reprogramming efficiency, mainly focused on removing repressive epigenetic marks such as histone methylation from the somatic nucleus. Herein we used the specific and non-toxic chemical probe UNC0638 to inhibit the catalytic activity of the histone methyltransferases EHMT1 and EHMT2. Either the donor cell (before reconstruction) or the early embryo was exposed to the probe to assess its effect on developmental rates and epigenetic marks. First, we showed that the treatment of bovine fibroblasts with UNC0638 did mitigate the levels of H3K9me2. Moreover, H3K9me2 levels were decreased in cloned embryos regardless of treating either donor cells or early embryos with UNC0638. Additional epigenetic marks such as H3K9me3, 5mC, and 5hmC were also affected by the UNC0638 treatment. Therefore, the use of UNC0638 did diminish the levels of H3K9me2 and H3K9me3 in SCNT-derived blastocysts, but this was unable to improve their preimplantation development. These results indicate that the specific reduction of H3K9me2 by inhibiting EHMT1/2 during nuclear reprogramming impacts the levels of H3K9me3, 5mC, and 5hmC in preimplantation bovine embryos. (AU)

FAPESP's process: 12/50533-2 - GIFT: genomic improvement of fertilization traits in Danish and Brazilian cattle
Grantee:Marcelo Fábio Gouveia Nogueira
Support type: Research Projects - Thematic Grants
FAPESP's process: 13/07160-3 - Influence of the 5-hydroxymethylcytosine on Nuclear Reprogramming of Bovines
Grantee:Rafael Vilar Sampaio
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 15/08807-6 - H3K9 methylation as regulator of epigenetic memory on bovine nuclear reprograming.
Grantee:Rafael Vilar Sampaio
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 14/50947-7 - INCT 2014: in Stem Cell and Cell Therapy
Grantee:Dimas Tadeu Covas
Support type: Research Projects - Thematic Grants
FAPESP's process: 15/25111-5 - Analysis and modulation of H3K9 methylation in bovine somatic cells
Grantee:Rafael Vilar Sampaio
Support type: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 14/21034-3 - Intra and intercellular routes during foliculogenesis and in vivo and in vitro oocyte maturation
Grantee:Felipe Perecin
Support type: Regular Research Grants
FAPESP's process: 14/22887-0 - Cell-secreted vesicles containing miRNAs modulate epigenetic changes during in vitro culture of bovine gametes and embryos
Grantee:Juliano Coelho da Silveira
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
Grantee:Dimas Tadeu Covas
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC