Aberrant patterns of X chromosome inactivation in bovine clones.
In mammals, epigenetic marks on the X chromosomes are involved in dosage compensation. Specifically, they are required for X chromosome inactivation (XCI), the random transcriptional silencing of one of the two X chromosomes in female cells during late blastocyst development. During natural reproduction, both X chromosomes are active in the female zygote. In somatic-cell cloning, however, the cloned embryos receive one active (Xa) and one inactive (Xi) X chromosome from the donor cells. Patterns of XCIhave been reported normal in cloned mice, but have yet to be investigated in other species. We examined allele-specific expression of the X-linked monoamine oxidase type A (MAOA) gene and the expression of nine additional X-linked genes in nine cloned XX calves. We found aberrant expression patterns in nine of ten X-linked genes and hypomethylation of Xist in organs of deceased clones. Analysis of MAOA expression in bovine placentae from natural reproduction revealed imprinted XCI with preferential inactivation of the paternal X chromosome. In contrast, we found random XCI in placentae of the deceased clones but completely skewed XCI in that of live clones. Thus, incomplete nuclear reprogramming may generate abnormal epigenetic marks on the X chromosomes of cloned cattle, affecting both random and imprinted XCI.
Xue
Fei
F
Department of Animal Science and Center for Regenerative Biology, University of Connecticut, Storrs, Connecticut 06269, USA.
Tian
X Cindy
XC
Du
Fuliang
F
Kubota
Chikara
C
Taneja
Maneesh
M
Dinnyes
Andras
A
Dai
Yunping
Y
Levine
Howard
H
Pereira
Lygia V
LV
Yang
Xiangzhong
X
D000818:Animals; D002417:Cattle; D019976:Cloning, Organism; D019175:DNA Methylation; D004303:Dosage Compensation, Genetic; D005260:Female; D008969:Molecular Sequence Data; D008995:Monoamine Oxidase / Q000235:genetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014960:X Chromosome / Q000235:genetics*
D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors; C077885:XIST non-coding RNA; D008995:Monoamine Oxidase