A new Xist allele driven by a constitutively active promoter is dominated by Xist locus environment and exhibits the parent-of-origin effects.
The dosage difference of X-linked genes between the sexes in mammals is compensated for by genetic inactivation of one of the X chromosomes in XX females. A noncoding RNA transcribed from the Xist gene at the onset of X chromosome inactivation coats the X chromosome in cis and induces chromosome-wide heterochromatinization. Here, we report a new Xist allele (Xist(CAG)) driven by a CAG promoter, which is known to be constitutively active in many types of cells. The paternal transmission of Xist(CAG) resulted in the preferential inactivation of the targeted paternal X (Xp) not only in the extra-embryonic but also the embryonic lineage, whereas maternal transmission ended with embryonic lethality at the early postimplantation stage with a phenotype that resembled mutant embryos carrying a maternal deficiency in Tsix, an antisense negative regulator of Xist, in both sexes. Interestingly, we found that the upregulation of Xist(CAG) in preimplantation embryos temporally differed depending on its parental origin: its expression started at the 4- to 8-cell stages when paternally inherited, and Xist(CAG) was upregulated at the blastocyst stage when maternally inherited. This might indicate that the Xist locus on Xp is permissive to transcription, but the Xist locus on the maternal X (Xm) is not. We extrapolated from these findings that the maternal Xist allele might manifest a chromatin structure inaccessible by transcription factors relative to the paternal allele. This might underlie the mechanism for the maternal repression of Xist at the early cleavage stage when Tsix expression has not yet occurred on Xm.
Division of Molecular Genetics, National Institute of Genetics, Research Organization of Information and Systems, 1111 Yata, Mishima 411-8540, Japan.
Yuko
Y
Amakawa
Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu-University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan Department of Advanced Bioscience, Graduate School of Agriculture, Kinki University, 3327-204, Nakamachi, Nara 631-8505, Japan.
Yuka
Y
Sakata
Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu-University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Yuko
Y
Hoki
Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Satoru
S
Arata
Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Seiji
S
Shioda
Division of Molecular Genetics, National Institute of Genetics, Research Organization of Information and Systems, 1111 Yata, Mishima 411-8540, Japan.
Tatsuo
T
Fukagawa
Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu-University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Hiroyuki
H
Sasaki
Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu-University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan Department of Advanced Bioscience, Graduate School of Agriculture, Kinki University, 3327-204, Nakamachi, Nara 631-8505, Japan tsado@nara.kindai.ac.jp.
Takashi
T
Sado
D000483:Alleles; D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D056426:Genetic Loci; D005854:Germ Cells / Q000378:metabolism; D040582:Inheritance Patterns / Q000235:genetics; D051379:Mice; D009154:Mutation / Q000235:genetics; D009866:Oogenesis; D010641:Phenotype; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D014960:X Chromosome / Q000235:genetics; D049951:X Chromosome Inactivation / Q000235:genetics
D062085:RNA, Long Noncoding; C465658:Tsix transcript, mouse; C077885:XIST non-coding RNA
Chromatin; Epigenetics; Mouse; X chromosome