Regulation of imprinted X-chromosome inactivation in mice by Tsix

T. Sado, Z. Wang, Hiroyuki Sasaki, E. Li

Research output: Contribution to journalArticle

238 Citations (Scopus)

Abstract

In mammals, X-chromosome inactivation is imprinted in the extra-embryonic lineages with paternal X chromosome being preferentially inactivated. In this study, we investigate the role of Tsix, the antisense transcript from the Xist locus, in regulation of Xist expression and X-inactivation. We show that Tsix is transcribed from two putative promoters and its transcripts are processed. Expression of Tsix is first detected in blastocysts and is imprinted with only the maternal allele transcribed. The imprinted expression of Tsix persists in the extra-embryonic tissues after implantation, but is erased in embryonic tissues. To investigate the function of Tsix in X-inactivation, we disrupted Tsix by insertion of an IRESβgeo cassette in the second exon, which blocked transcripts from both promoters. While disruption of the paternal Tsix allele has no adverse effects on embryonic development, inheritance of a disrupted maternal allele results in ectopic Xist expression and early embryonic lethality, owing to inactivation of both X chromosomes in females and single X chromosome in males. Further, early developmental defects of female embryos with maternal transmission of Tsix mutation can be rescued by paternal inheritance of the Xist deletion. These results provide genetic evidence that Tsix plays a crucial role in maintaining Xist silencing in cis and in regulation of imprinted X-inactivation in the extra-embryonic tissues.

Original languageEnglish
Pages (from-to)1275-1286
Number of pages12
JournalDevelopment
Volume128
Issue number8
Publication statusPublished - May 17 2001
Externally publishedYes

Fingerprint

X Chromosome Inactivation
Alleles
Mothers
X Chromosome
Blastocyst
Embryonic Development
Mammals
Exons
Embryonic Structures
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Cite this

Sado, T., Wang, Z., Sasaki, H., & Li, E. (2001). Regulation of imprinted X-chromosome inactivation in mice by Tsix. Development, 128(8), 1275-1286.

Regulation of imprinted X-chromosome inactivation in mice by Tsix. / Sado, T.; Wang, Z.; Sasaki, Hiroyuki; Li, E.

In: Development, Vol. 128, No. 8, 17.05.2001, p. 1275-1286.

Research output: Contribution to journalArticle

Sado, T, Wang, Z, Sasaki, H & Li, E 2001, 'Regulation of imprinted X-chromosome inactivation in mice by Tsix', Development, vol. 128, no. 8, pp. 1275-1286.
Sado, T. ; Wang, Z. ; Sasaki, Hiroyuki ; Li, E. / Regulation of imprinted X-chromosome inactivation in mice by Tsix. In: Development. 2001 ; Vol. 128, No. 8. pp. 1275-1286.
@article{bd6c484ed0dd413e850ac24ff10e40aa,
title = "Regulation of imprinted X-chromosome inactivation in mice by Tsix",
abstract = "In mammals, X-chromosome inactivation is imprinted in the extra-embryonic lineages with paternal X chromosome being preferentially inactivated. In this study, we investigate the role of Tsix, the antisense transcript from the Xist locus, in regulation of Xist expression and X-inactivation. We show that Tsix is transcribed from two putative promoters and its transcripts are processed. Expression of Tsix is first detected in blastocysts and is imprinted with only the maternal allele transcribed. The imprinted expression of Tsix persists in the extra-embryonic tissues after implantation, but is erased in embryonic tissues. To investigate the function of Tsix in X-inactivation, we disrupted Tsix by insertion of an IRESβgeo cassette in the second exon, which blocked transcripts from both promoters. While disruption of the paternal Tsix allele has no adverse effects on embryonic development, inheritance of a disrupted maternal allele results in ectopic Xist expression and early embryonic lethality, owing to inactivation of both X chromosomes in females and single X chromosome in males. Further, early developmental defects of female embryos with maternal transmission of Tsix mutation can be rescued by paternal inheritance of the Xist deletion. These results provide genetic evidence that Tsix plays a crucial role in maintaining Xist silencing in cis and in regulation of imprinted X-inactivation in the extra-embryonic tissues.",
author = "T. Sado and Z. Wang and Hiroyuki Sasaki and E. Li",
year = "2001",
month = "5",
day = "17",
language = "English",
volume = "128",
pages = "1275--1286",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "8",

}

TY - JOUR

T1 - Regulation of imprinted X-chromosome inactivation in mice by Tsix

AU - Sado, T.

AU - Wang, Z.

AU - Sasaki, Hiroyuki

AU - Li, E.

PY - 2001/5/17

Y1 - 2001/5/17

N2 - In mammals, X-chromosome inactivation is imprinted in the extra-embryonic lineages with paternal X chromosome being preferentially inactivated. In this study, we investigate the role of Tsix, the antisense transcript from the Xist locus, in regulation of Xist expression and X-inactivation. We show that Tsix is transcribed from two putative promoters and its transcripts are processed. Expression of Tsix is first detected in blastocysts and is imprinted with only the maternal allele transcribed. The imprinted expression of Tsix persists in the extra-embryonic tissues after implantation, but is erased in embryonic tissues. To investigate the function of Tsix in X-inactivation, we disrupted Tsix by insertion of an IRESβgeo cassette in the second exon, which blocked transcripts from both promoters. While disruption of the paternal Tsix allele has no adverse effects on embryonic development, inheritance of a disrupted maternal allele results in ectopic Xist expression and early embryonic lethality, owing to inactivation of both X chromosomes in females and single X chromosome in males. Further, early developmental defects of female embryos with maternal transmission of Tsix mutation can be rescued by paternal inheritance of the Xist deletion. These results provide genetic evidence that Tsix plays a crucial role in maintaining Xist silencing in cis and in regulation of imprinted X-inactivation in the extra-embryonic tissues.

AB - In mammals, X-chromosome inactivation is imprinted in the extra-embryonic lineages with paternal X chromosome being preferentially inactivated. In this study, we investigate the role of Tsix, the antisense transcript from the Xist locus, in regulation of Xist expression and X-inactivation. We show that Tsix is transcribed from two putative promoters and its transcripts are processed. Expression of Tsix is first detected in blastocysts and is imprinted with only the maternal allele transcribed. The imprinted expression of Tsix persists in the extra-embryonic tissues after implantation, but is erased in embryonic tissues. To investigate the function of Tsix in X-inactivation, we disrupted Tsix by insertion of an IRESβgeo cassette in the second exon, which blocked transcripts from both promoters. While disruption of the paternal Tsix allele has no adverse effects on embryonic development, inheritance of a disrupted maternal allele results in ectopic Xist expression and early embryonic lethality, owing to inactivation of both X chromosomes in females and single X chromosome in males. Further, early developmental defects of female embryos with maternal transmission of Tsix mutation can be rescued by paternal inheritance of the Xist deletion. These results provide genetic evidence that Tsix plays a crucial role in maintaining Xist silencing in cis and in regulation of imprinted X-inactivation in the extra-embryonic tissues.

UR - http://www.scopus.com/inward/record.url?scp=0035030004&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035030004&partnerID=8YFLogxK

M3 - Article

C2 - 11262229

AN - SCOPUS:0035030004

VL - 128

SP - 1275

EP - 1286

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 8

ER -