Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer.
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.
Inoue
Kimiko
K
BioResource Center, RIKEN, 305-0024 Tsukuba, Japan.
Kohda
Takashi
T
Sugimoto
Michihiko
M
Sado
Takashi
T
Ogonuki
Narumi
N
Matoba
Shogo
S
Shiura
Hirosuke
H
Ikeda
Rieko
R
Mochida
Keiji
K
Fujii
Takashi
T
Sawai
Ken
K
Otte
Arie P
AP
Tian
X Cindy
XC
Yang
Xiangzhong
X
Ishino
Fumitoshi
F
Abe
Kuniya
K
Ogura
Atsuo
A
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
D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA