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Inhibition of Class IIb Histone Deacetylase Significantly Improves Cloning Efficiency.pdf

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Inhibition of Class IIb Histone Deacetylase Significantly Improves Cloning Efficiency

BIOLOGY OF REPRODUCTION 83, 929–937 (2010) Published online before print 4 August 2010. DOI 10.1095/biolreprod.110.085282 Inhibition of Class IIb Histone Deacetylase Significantly Improves Cloning Efficiency in Mice1 Tetsuo Ono,3,4 Chong Li,3,5 Eiji Mizutani,3 Yukari Terashita,3,6 Kazuo Yamagata,3 and Teruhiko Wakayama2,3,4,5 Laboratory for Genomic Reprogramming,3 RIKEN Center for Developmental Biology, Kobe, Japan Department of Medical Science,4 Graduate School of Medicine, Kyoto University, Kyoto, Japan Department of Bioscience,5 Graduate School of Science and Technology, Kwansei Gakuin University, Sanda, Japan Laboratory of Animal Reproduction,6 Graduate School of Agricultural Science, Tohoku University, Sendai, Japan ABSTRACT Since the first mouse clone was produced by somatic cell nuclear transfer, the success rate of cloning in mice has been extremely low. Some histone deacetylase inhibitors, such as trichostatin A and scriptaid, have improved the full-term development of mouse clones significantly, but the mechanisms allowing for this are unclear. Here, we found that two other specific inhibitors, suberoylanilide hydroxamic acid and oxam- flatin, could also reduce the rate of apoptosis in blastocysts, improve the full-term development of cloned mice, and increase establishment of nuclear transfer-generated embryonic stem cell lines significantly without leading to obvious abnormalities. However, another inhibitor, valproic acid, could not improve cloning efficiency. Suberoylanilide hydroxamic acid, oxamflatin, trichostatin A, and scriptaid are inhibitors for classes I and IIa/b histone deacetylase, whereas valproic acid is an inhibitor for classes I and IIa, suggesting that inhibiting class IIb histone deacetylase is an important step for reprogramming mouse cloning efficiency. clone, developmental biology, early development, embryo, HDACi, nuclear transfer, ntES cell, reprogramming INTRODUCTION The success of animal cloning by somatic cell nuclear transfer (