title: Trichostatin A improves histone acetylation in bovine somatic cell nuclear transfer early embryos.
abstract: Epigenetic aberrancies likely preclude correct and complete nuclear reprogramming following somatic cell nuclear transfer (SCNT), and may underlie the observed reduced viability of cloned embryos. In the present study, we tested the effects of the histone deacetylase inhibitor (HDACi), trichostatin A (TSA), on development and histone acetylation of cloned bovine preimplantation embryos. Our results indicated that treating activated reconstructed SCNT embryos with 50 nM TSA for 13 h produced eight-cell embryos with levels of acetylation of histone H4 at lysine 5 (AcH4K5) similar to fertilized counterparts and significantly greater than in control NT embryos (p < 0.005). Further, TSA treatment resulted in SCNT embryos with preimplantation developmental potential similar to fertilized counterparts, as no difference was observed in cleavage and blastocyst rates or in blastocyst total cell number (p > 0.05). Measurement of eight selected developmentally important genes in single blastocysts showed a similar expression profile among the three treatment groups, with the exception of Nanog, Cdx2, and DNMT3b, whose expression levels were higher in TSA-treated NT than in in vitro fertilized (IVF) embryos. Data presented herein demonstrate that TSA can improve at least one epigenetic mark in early cloned bovine embryos. However, evaluation of development to full-term is necessary to ascertain whether this effect reflects a true increase in developmental potential.
authors.affiliation: Cellular Reprogramming Laboratory, Department of Animal Science, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Iager
authors.forename: Neli P
authors.initials: NP
authors.lastname: Ragina
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Ross
authors.forename: Zeki
authors.initials: Z
authors.lastname: Beyhan
authors.forename: Kerrianne
authors.initials: K
authors.lastname: Cunniff
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Rodriguez
authors.forename: Jose B
authors.initials: JB
authors.lastname: Cibelli
mesh_terms: D000107:Acetylation; D000818:Animals; D002417:Cattle; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D053652:Nuclear Transfer Techniques; D011247:Pregnancy
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A