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J. Biol. Chem., Vol. 281, Issue 9, 6048-6057, March 3, 2006

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Inheritable Histone H4 Acetylation of Somatic Chromatins in Cloned Embryos^*

Gabbine Wee, Deog-Bon Koo, Bong-Seok Song, Ji-Su Kim, Man-Jong Kang, Seung-Ju Moon, Yong-Kook Kang, Kyung-Kwang Lee, and Yong-Mahn Han¹

From the Laboratory of Development and Differentiation, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Korea and the Department of Animal Science, Chonnam National University, Gwangju 500-757, Korea

A viable cloned animal indicates that epigenetic status of the differentiated cell nucleus is reprogrammed to an embryonic totipotent state. However, molecular events regarding epigenetic reprogramming of the somatic chromatin are poorly understood. Here we provide new insight that somatic chromatins are refractory to reprogramming of histone acetylation during early development. A low level of acetylated histone H4-lysine 5 (AcH4K5) of the somatic chromatin was sustained at the pronuclear stage. Unlike in vitro fertilized (IVF) embryos, the AcH4K5 level remarkably reduced at the 8-cell stage in cloned bovine embryos. The AcH4K5 status of somatic chromatins transmitted to cloned and even recloned embryos. Differences of AcH4K5 signal intensity were more distinguishable in the metaphase chromosomes between IVF and cloned embryos. Two imprinted genes, Ndn and Xist, were aberrantly expressed in cloned embryos as compared with IVF embryos, which is partly associated with the AcH4K5 signal intensity. Our findings suggest that abnormal epigenetic reprogramming in cloned embryos may be because of a memory mechanism, the epigenetic status itself of somatic chromatins.

Received for publication, October 19, 2005 , and in revised form, December 19, 2005.

^* This work was supported by National Research Laboratory Program Grant KNM0100525 and Stem Cell Research Center of the 21st Century Frontier Research Program SC2090, BioGreen 21 Project ABM0020514, and the Research Project on the Production of Bio-organs Grant ABC060512, Korea. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1 and Table S1.

¹ To whom correspondence should be addressed: 52 Eoeun-dong, Yuseong, Daejeon 305-806, Korea. Tel.: 82-42-860-4429; Fax: 82-42-860-4608; E-mail: ymhan{at}kribb.re.kr.

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