Treatment of Nuclear-Donor Cells or Cloned Zygotes with Chromatin-Modifying Agents Increases Histone Acetylation But Does Not Improve Full-Term Development of Cloned Cattle

Author(s)

Sangalli, Juliano Rodrigues ^[1] ; Camara de Bem, Tiago Henrique ^[1] ; Perecin, Felipe ^[1] ; Chiaratti, Marcos Roberto ^[1] ; Oliveira, Lilian de Jesus ^[1] ; de Araujo, Reno Roldi ^[1] ; Valim Pimentel, Jose Rodrigo ^[1] ; Smith, Lawrence Charles ^[2] ; Meirelles, Flavio Vieira ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Ciencias Basicas, Fac Zootecnia & Engn Alimentos, BR-13635900 Pirassununga, SP - Brazil

^[2] Univ Montreal, Fac Med Vet, Ctr Rech Reprod Anim, St Hyacinthe, PQ J2S 7C6 - Canada

• Document type: Journal article
• Source: CELLULAR REPROGRAMMING; v. 14, n. 3, p. 235-247, JUN 2012.
• Web of Science Citations: 27

Abstract

Although somatic cell nuclear transfer (SCNT) is a promising tool, its potential use is hampered by the high mortality rates during the development to term of cloned offspring. Abnormal epigenetic reprogramming of donor nuclei after SCNT is thought to be the main cause of this low efficiency. We hypothesized that chromatin-modifying agents (CMAs) targeting chromatin acetylation and DNA methylation could alter the chromatin configuration and turn them more amenable to reprogramming. Thus, bovine fibroblasts were treated with 5-aza-2'-deoxycytidine (AZA) plus trichostatin (TSA) or hydralazine (HH) plus valproic acid (VPA) whereas, in another trial, cloned bovine zygotes were treated with TSA. The treatment of fibroblasts with either AZA + TSA or HH + VPA increased histone acetylation, but did not affect the level of DNA methylation. However, treatment with HH + VPA decreased cellular viability and proliferation. The use of these cells as nuclear donors showed no positive effect on pre- and postimplantation development. Regarding the treatment of cloned zygotes with TSA, treated one-cell embryos showed an increase in the acetylation patterns, but not in the level of DNA methylation. Moreover, this treatment revealed no positive effect on pre- and postimplantation development. This work provides evidence the treatment of either nuclear donor cells or cloned zygotes with CMAs has no positive effect on pre- and postimplantation development of cloned cattle. (AU)

• FAPESP's process: 09/06689-5 - Use of chromatin modification agents in somatic cell nuclear transfer in cattle
• Grantee: Juliano Rodrigues Sangalli
• Support Opportunities: Scholarships in Brazil - Master