Xist imprinting is promoted by the hemizygous (unpaired) state in the male germ line.
The long noncoding X-inactivation-specific transcript (Xist gene) is responsible for mammalian X-chromosome dosage compensation between the sexes, the process by which one of the two X chromosomes is inactivated in the female soma. Xist is essential for both the random and imprinted forms of X-chromosome inactivation. In the imprinted form, Xist is paternally marked to be expressed in female embryos. To investigate the mechanism of Xist imprinting, we introduce Xist transgenes (Tg) into the male germ line. Although ectopic high-level Xist expression on autosomes can be compatible with viability, transgenic animals demonstrate reduced fitness, subfertility, defective meiotic pairing, and other germ-cell abnormalities. In the progeny, paternal-specific expression is recapitulated by the 200-kb Xist Tg. However, Xist imprinting occurs efficiently only when it is in an unpaired or unpartnered state during male meiosis. When transmitted from a hemizygous father (+/Tg), the Xist Tg demonstrates paternal-specific expression in the early embryo. When transmitted by a homozygous father (Tg/Tg), the Tg fails to show imprinted expression. Thus, Xist imprinting is directed by sequences within a 200-kb X-linked region, and the hemizygous (unpaired) state of the Xist region promotes its imprinting in the male germ line.
Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02114; Department of Developmental and Cell Biology, School of Biological Sciences, University of California, Irvine, CA 92697;
Sha
S
Sun
Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02114;
Bernhard
B
Payer
Division of Reproductive Sciences, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229;
Satoshi
S
Namekawa
Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02114;
Jee Young
JY
An
Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02114;
William
W
Press
Department of Developmental and Cell Biology, School of Biological Sciences, University of California, Irvine, CA 92697;
Jovani
J
Catalan-Dibene
Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02114;
Hongjae
H
Sunwoo
Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02114; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02114 lee@molbio.mgh.harvard.edu.
Jeannie T
JT
Lee
D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D018392:Genomic Imprinting; D005854:Germ Cells / Q000378:metabolism*; D057898:Hemizygote; D007248:Infertility, Male / Q000235:genetics / Q000473:pathology; D008297:Male; D008822:Mice, Transgenic; D010641:Phenotype; D062085:RNA, Long Noncoding / Q000138:chemical synthesis / Q000235:genetics* / Q000378:metabolism; D019076:Transgenes
D062085:RNA, Long Noncoding; C077885:XIST non-coding RNA
X inactivation; Xist; imprinting; meiotic silencing by unpaired DNA; transgenerational inheritance