DOI: 10.1126/science.1113673. Regulation of X-Chromosome Counting by <i>Tsix</i> and <i>Xite</i> Sequences

Regulation of X-Chromosome Counting by Tsix and Xite Sequences

10.1126/science.1113673

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

In mammals, X-inactivation establishes X-chromosome dosage parity between males and females. How X-chromosome counting regulates this process remains elusive, because neither the hypothesized inactivation “blocking factor” nor the required cis-elements have been defined. Here, a mouse knockout and transgenic analysis identified DNA sequences within the noncoding Tsix and Xite genes as numerators. Homozygous deficiency of Tsix resulted in “chaotic choice” and a variable number of inactive X's, whereas overdosage of Tsix / Xite inhibited X-inactivation. Thus, counting was affected by specific Tsix / Xite mutations, suggesting that counting is genetically separable from but molecularly coupled to choice. The mutations affect XX and XY cells differently, demonstrating that counting and choice are regulated not by one “blocking factor,” but by both a “blocking” and a “competence” factor.

Bibliography

Lee, J. T. (2005). Regulation of X-Chromosome Counting by Tsix and Xite Sequences. Science, 309(5735), 768â771.

Authors 1

Jeannie T. Lee (first)

References 15 Referenced 117

10.1038/190372a0
10.1016/S0092-8674(00)80061-6
10.1016/S1097-2765(03)00063-7
M. F. Lyon, Biol. Rev. Camb. Philos. Soc.47, 1 (1972). (10.1111/j.1469-185X.1972.tb00969.x) / Biol. Rev. Camb. Philos. Soc. (1972)
S. Rastan, J. Embryol. Exp. Morphol.78, 1 (1983). / J. Embryol. Exp. Morphol. (1983)
J. T. Lee, W. M. Strauss, J. A. Dausman, R. Jaenisch, Cell86, 83 (1996). (10.1016/S0092-8674(00)80079-3) / Cell (1996)
10.1128/MCB.19.4.3156
10.1073/pnas.96.7.3836
P. Clerc, P. Avner, Nat. Genet.19, 249 (1998). (10.1038/924) / Nat. Genet. (1998)
10.1038/sj.emboj.7600071
10.1038/ng939
10.1016/0092-8674(92)90520-M
10.1038/379131a0
N. Stavropoulos, R. K. Rowntree, J. T. Lee, Mol. Cell. Biol.25, 2757 (2005). (10.1128/MCB.25.7.2757-2769.2005) / Mol. Cell. Biol. (2005)
I thank Y. Ogawa for pSx7 and pXite (pDNT1); N. Xu for pTsx; L. F. Zhang D. E. Cohen N. Xu B. K. Sun R. J. Spencer D. Tian and J. E. Kirby for critical reading; and all lab members for stimulating discussion. J.T.L. is an Investigator of the Howard Hughes Medical Institute and is supported by the NIH (RO1-GM58839).

Dates

Type	When
Created	20 years, 1 month ago (July 28, 2005, 5:43 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 9:42 p.m.)
Indexed	1 month ago (July 24, 2025, 7:32 a.m.)
Issued	20 years ago (July 29, 2005)
Published	20 years ago (July 29, 2005)
Published Print	20 years ago (July 29, 2005)

Funders 0

None

BibTeX

@article{Lee_2005, title={Regulation of X-Chromosome Counting by Tsix and Xite Sequences}, volume={309}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1113673}, DOI={10.1126/science.1113673}, number={5735}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Lee, Jeannie T.}, year={2005}, month=jul, pages={768–771} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        24
      ]
    ],
    "date-time": "2025-07-24T11:32:47Z",
    "timestamp": 1753356767568
  },
  "reference-count": 15,
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "issue": "5735",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2005,
        7,
        29
      ]
    ]
  },
  "abstract": "<jats:p>\n            In mammals, X-inactivation establishes X-chromosome dosage parity between males and females. How X-chromosome counting regulates this process remains elusive, because neither the hypothesized inactivation \u201cblocking factor\u201d nor the required cis-elements have been defined. Here, a mouse knockout and transgenic analysis identified DNA sequences within the noncoding\n            <jats:italic>Tsix</jats:italic>\n            and\n            <jats:italic>Xite</jats:italic>\n            genes as numerators. Homozygous deficiency of\n            <jats:italic>Tsix</jats:italic>\n            resulted in \u201cchaotic choice\u201d and a variable number of inactive X's, whereas overdosage of\n            <jats:italic>Tsix</jats:italic>\n            /\n            <jats:italic>Xite</jats:italic>\n            inhibited X-inactivation. Thus, counting was affected by specific\n            <jats:italic>Tsix</jats:italic>\n            /\n            <jats:italic>Xite</jats:italic>\n            mutations, suggesting that counting is genetically separable from but molecularly coupled to choice. The mutations affect XX and XY cells differently, demonstrating that counting and choice are regulated not by one \u201cblocking factor,\u201d but by both a \u201cblocking\u201d and a \u201ccompetence\u201d factor.\n          </jats:p>",
  "DOI": "10.1126/science.1113673",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2005,
        7,
        28
      ]
    ],
    "date-time": "2005-07-28T21:43:39Z",
    "timestamp": 1122587019000
  },
  "page": "768-771",
  "source": "Crossref",
  "is-referenced-by-count": 117,
  "title": "Regulation of X-Chromosome Counting by\n            <i>Tsix</i>\n            and\n            <i>Xite</i>\n            Sequences",
  "prefix": "10.1126",
  "volume": "309",
  "author": [
    {
      "given": "Jeannie T.",
      "family": "Lee",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School Boston, MA 02114, USA."
        }
      ]
    }
  ],
  "member": "221",
  "reference": [
    {
      "key": "e_1_3_1_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/190372a0"
    },
    {
      "key": "e_1_3_1_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)80061-6"
    },
    {
      "key": "e_1_3_1_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1097-2765(03)00063-7"
    },
    {
      "key": "e_1_3_1_5_2",
      "doi-asserted-by": "crossref",
      "first-page": "1",
      "DOI": "10.1111/j.1469-185X.1972.tb00969.x",
      "volume": "47",
      "year": "1972",
      "unstructured": "M. F. Lyon, Biol. Rev. Camb. Philos. Soc.47, 1 (1972).",
      "journal-title": "Biol. Rev. Camb. Philos. Soc."
    },
    {
      "key": "e_1_3_1_6_2",
      "first-page": "1",
      "volume": "78",
      "year": "1983",
      "unstructured": "S. Rastan, J. Embryol. Exp. Morphol.78, 1 (1983).",
      "journal-title": "J. Embryol. Exp. Morphol."
    },
    {
      "key": "e_1_3_1_7_2",
      "doi-asserted-by": "crossref",
      "first-page": "83",
      "DOI": "10.1016/S0092-8674(00)80079-3",
      "volume": "86",
      "year": "1996",
      "unstructured": "J. T. Lee, W. M. Strauss, J. A. Dausman, R. Jaenisch, Cell86, 83 (1996).",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_1_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.19.4.3156"
    },
    {
      "key": "e_1_3_1_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.96.7.3836"
    },
    {
      "key": "e_1_3_1_10_2",
      "doi-asserted-by": "crossref",
      "first-page": "249",
      "DOI": "10.1038/924",
      "volume": "19",
      "year": "1998",
      "unstructured": "P. Clerc, P. Avner, Nat. Genet.19, 249 (1998).",
      "journal-title": "Nat. Genet."
    },
    {
      "key": "e_1_3_1_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.emboj.7600071"
    },
    {
      "key": "e_1_3_1_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ng939"
    },
    {
      "key": "e_1_3_1_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(92)90520-M"
    },
    {
      "key": "e_1_3_1_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/379131a0"
    },
    {
      "key": "e_1_3_1_15_2",
      "doi-asserted-by": "crossref",
      "first-page": "2757",
      "DOI": "10.1128/MCB.25.7.2757-2769.2005",
      "volume": "25",
      "year": "2005",
      "unstructured": "N. Stavropoulos, R. K. Rowntree, J. T. Lee, Mol. Cell. Biol.25, 2757 (2005).",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "e_1_3_1_16_2",
      "unstructured": "I thank Y. Ogawa for pSx7 and pXite (pDNT1); N. Xu for pTsx; L. F. Zhang D. E. Cohen N. Xu B. K. Sun R. J. Spencer D. Tian and J. E. Kirby for critical reading; and all lab members for stimulating discussion. J.T.L. is an Investigator of the Howard Hughes Medical Institute and is supported by the NIH (RO1-GM58839)."
    }
  ],
  "container-title": "Science",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://www.science.org/doi/pdf/10.1126/science.1113673",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        1,
        10
      ]
    ],
    "date-time": "2024-01-10T02:42:37Z",
    "timestamp": 1704854557000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.science.org/doi/10.1126/science.1113673"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2005,
        7,
        29
      ]
    ]
  },
  "references-count": 15,
  "journal-issue": {
    "issue": "5735",
    "published-print": {
      "date-parts": [
        [
          2005,
          7,
          29
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1126/science.1113673"
  ],
  "URL": "http://dx.doi.org/10.1126/science.1113673",
  "relation": {},
  "ISSN": [
    "0036-8075",
    "1095-9203"
  ],
  "subject": [],
  "container-title-short": "Science",
  "published": {
    "date-parts": [
      [
        2005,
        7,
        29
      ]
    ]
  }
}