title: Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer.
abstract: Cloning mammals by means of somatic cell nuclear transfer (SCNT) is highly inefficient because of erroneous reprogramming of the donor genome. Reprogramming errors appear to arise randomly, but the nature of nonrandom, SCNT-specific errors remains elusive. We found that Xist, a noncoding RNA that inactivates one of the two X chromosomes in females, was ectopically expressed from the active X (Xa) chromosome in cloned mouse embryos of both sexes. Deletion of Xist on Xa showed normal global gene expression and resulted in about an eight- to ninefold increase in cloning efficiency. We also identified an Xist-independent mechanism that specifically down-regulated a subset of X-linked genes through somatic-type repressive histone blocks. Thus, we have identified nonrandom reprogramming errors in mouse cloning that can be altered to improve the efficiency of SCNT methods.
authors.affiliation: BioResource Center, RIKEN, 305-0024 Tsukuba, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Inoue
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohda
authors.forename: Michihiko
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Sado
authors.forename: Narumi
authors.initials: N
authors.lastname: Ogonuki
authors.forename: Shogo
authors.initials: S
authors.lastname: Matoba
authors.forename: Hirosuke
authors.initials: H
authors.lastname: Shiura
authors.forename: Rieko
authors.initials: R
authors.lastname: Ikeda
authors.forename: Keiji
authors.initials: K
authors.lastname: Mochida
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujii
authors.forename: Ken
authors.initials: K
authors.lastname: Sawai
authors.forename: Arie P
authors.initials: AP
authors.lastname: Otte
authors.forename: X Cindy
authors.initials: XC
authors.lastname: Tian
authors.forename: Xiangzhong
authors.initials: X
authors.lastname: Yang
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Ishino
authors.forename: Kuniya
authors.initials: K
authors.lastname: Abe
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
mesh_terms: D000818:Animals; D019976:Cloning, Organism / Q000379:methods*; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D053652:Nuclear Transfer Techniques; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014960:X Chromosome
chemical_list: D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA