DOI: 10.1083/jcb.200404107. Transcription-dependent spatial arrangements of CFTR and adjacent genes in human cell nuclei

Transcription-dependent spatial arrangements of CFTR and adjacent genes in human cell nuclei

10.1083/jcb.200404107

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

We investigated in different human cell types nuclear positioning and transcriptional regulation of the functionally unrelated genes GASZ, CFTR, and CORTBP2, mapping to adjacent loci on human chromosome 7q31. When inactive, GASZ, CFTR, and CORTBP2 preferentially associated with the nuclear periphery and with perinuclear heterochromatin, whereas in their actively transcribed states the gene loci preferentially associated with euchromatin in the nuclear interior. Adjacent genes associated simultaneously with these distinct chromatin fractions localizing at different nuclear regions, in accordance with their individual transcriptional regulation. Although the nuclear localization of CFTR changed after altering its transcription levels, the transcriptional status of CFTR was not changed by driving this gene into a different nuclear environment. This implied that the transcriptional activity affected the nuclear positioning, and not vice versa. Together, the results show that small chromosomal subregions can display highly flexible nuclear organizations that are regulated at the level of individual genes in a transcription-dependent manner.

Bibliography

Zink, D., Amaral, M. D., Englmann, A., Lang, S., Clarke, L. A., Rudolph, C., Alt, F., Luther, K., Braz, C., Sadoni, N., Rosenecker, J., & Schindelhauer, D. (2004). Transcription-dependent spatial arrangements of CFTR and adjacent genes in human cell nuclei. The Journal of Cell Biology, 166(6), 815â825.

Authors 12

Daniele Zink (first)
Margarida D. Amaral (additional)
Andreas Englmann (additional)
Susanne Lang (additional)
Luka A. Clarke (additional)
Carsten Rudolph (additional)
Felix Alt (additional)
Kathrin Luther (additional)
Carla Braz (additional)
Nicolas Sadoni (additional)
Joseph Rosenecker (additional)
Dirk Schindelhauer (additional)

References 38 Referenced 229

{'key': '2023072906401366700_BIB1', 'first-page': '17', 'volume': '3 Suppl 2', 'year': '2004', 'journal-title': 'J. Cystic Fibrosis.'} / J. Cystic Fibrosis. (2004)
10.1101/gad.1102803 / Genes Dev. (2003)
10.1007/BF00291049 / Chromosoma. (1989)
10.1093/hmg/10.3.211 / Hum. Mol. Genet. (2001)
10.1016/S0092-8674(00)80472-9 / Cell. (1997)
10.1016/S1097-2765(00)80311-1 / Mol. Cell. (1999)
10.1038/35078577 / Nat. Cell Biol. (2001)
10.1006/geno.2001.6651 / Genomics. (2001)
10.1091/mbc.10.1.211 / Mol. Biol. Cell. (1999)
10.1038/35066075 / Nat. Rev. Genet. (2001)
10.1101/SQB.1993.058.01.085 / Cold Spring Harb. Symp. Quant. Biol. (1993)
{'key': '2023072906401366700_BIB12'}
10.1083/jcb.145.6.1119 / J. Cell Biol. (1999)
10.1083/jcb.135.6.1427 / J. Cell Biol. (1996)
10.1172/JCI117028 / J. Clin. Invest (1994)
10.1016/0962-8924(94)90180-5 / Trends Cell Biol. (1994)
10.1083/jcb.139.7.1597 / J. Cell Biol. (1997)
10.1002/j.1460-2075.1995.tb07151.x / EMBO J. (1995)
10.1016/S0092-8674(04)00171-0 / Cell. (2004)
10.1126/science.1068768 / Science. (2002)
10.1038/331358a0 / Nature. (1988)
10.1083/jcb.200207115 / J. Cell Biol. (2002)
10.1083/jcb.200111071 / J. Cell Biol. (2002)
10.1038/ng843 / Nat. Genet. (2002)
10.1242/jcs.114.18.3297 / J. Cell Sci. (2001)
10.1083/jcb.135.6.1685 / J. Cell Biol. (1996)
10.1083/jcb.146.6.1211 / J. Cell Biol. (1999)
10.1023/A:1026799818566 / Chromosome Res. (2001)
10.1101/gad.14.8.940 / Genes Dev. (2000)
10.1038/ni0901-848 / Nat. Immunol. (2001)
10.1006/excr.2002.5513 / Exp. Cell Res. (2002)
10.1038/35055033 / Nat. Cell Biol. (2001)
10.1083/jcb.147.1.13 / J. Cell Biol. (1999)
10.1242/jcs.113.9.1565 / J. Cell Sci. (2000)
10.1006/excr.2001.5400 / Exp. Cell Res. (2002)
{'key': '2023072906401366700_BIB36', 'first-page': '1168', 'volume': '16', 'year': '2002', 'journal-title': 'Mol. Endocrinol.'} / Mol. Endocrinol. (2002)
10.1007/s004390050686 / Hum. Genet. (1998)
10.1016/S1046-2023(02)00289-X / Methods. (2003)

Dates

Type	When
Created	20 years, 11 months ago (Sept. 13, 2004, 3:12 p.m.)
Deposited	2 years, 1 month ago (July 29, 2023, 2:41 a.m.)
Indexed	7 minutes ago (Aug. 30, 2025, 7:26 p.m.)
Issued	20 years, 11 months ago (Sept. 13, 2004)
Published	20 years, 11 months ago (Sept. 13, 2004)
Published Online	20 years, 11 months ago (Sept. 13, 2004)
Published Print	20 years, 11 months ago (Sept. 13, 2004)

Funders 0

None

BibTeX

@article{Zink_2004, title={Transcription-dependent spatial arrangements of CFTR and adjacent genes in human cell nuclei}, volume={166}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200404107}, DOI={10.1083/jcb.200404107}, number={6}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Zink, Daniele and Amaral, Margarida D. and Englmann, Andreas and Lang, Susanne and Clarke, Luka A. and Rudolph, Carsten and Alt, Felix and Luther, Kathrin and Braz, Carla and Sadoni, Nicolas and Rosenecker, Joseph and Schindelhauer, Dirk}, year={2004}, month=sep, pages={815–825} }

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      "first-page": "17",
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    {
      "key": "2023072906401366700_BIB2",
      "doi-asserted-by": "crossref",
      "first-page": "1855",
      "DOI": "10.1101/gad.1102803",
      "volume": "17",
      "year": "2003",
      "journal-title": "Genes Dev."
    },
    {
      "key": "2023072906401366700_BIB3",
      "doi-asserted-by": "crossref",
      "first-page": "129",
      "DOI": "10.1007/BF00291049",
      "volume": "98",
      "year": "1989",
      "journal-title": "Chromosoma."
    },
    {
      "key": "2023072906401366700_BIB4",
      "doi-asserted-by": "crossref",
      "first-page": "211",
      "DOI": "10.1093/hmg/10.3.211",
      "volume": "10",
      "year": "2001",
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    },
    {
      "key": "2023072906401366700_BIB5",
      "doi-asserted-by": "crossref",
      "first-page": "845",
      "DOI": "10.1016/S0092-8674(00)80472-9",
      "volume": "91",
      "year": "1997",
      "journal-title": "Cell."
    },
    {
      "key": "2023072906401366700_BIB6",
      "doi-asserted-by": "crossref",
      "first-page": "207",
      "DOI": "10.1016/S1097-2765(00)80311-1",
      "volume": "3",
      "year": "1999",
      "journal-title": "Mol. Cell."
    },
    {
      "key": "2023072906401366700_BIB7",
      "doi-asserted-by": "crossref",
      "first-page": "602",
      "DOI": "10.1038/35078577",
      "volume": "3",
      "year": "2001",
      "journal-title": "Nat. Cell Biol."
    },
    {
      "key": "2023072906401366700_BIB8",
      "doi-asserted-by": "crossref",
      "first-page": "7",
      "DOI": "10.1006/geno.2001.6651",
      "volume": "78",
      "year": "2001",
      "journal-title": "Genomics."
    },
    {
      "key": "2023072906401366700_BIB9",
      "doi-asserted-by": "crossref",
      "first-page": "211",
      "DOI": "10.1091/mbc.10.1.211",
      "volume": "10",
      "year": "1999",
      "journal-title": "Mol. Biol. Cell."
    },
    {
      "key": "2023072906401366700_BIB10",
      "doi-asserted-by": "crossref",
      "first-page": "292",
      "DOI": "10.1038/35066075",
      "volume": "2",
      "year": "2001",
      "journal-title": "Nat. Rev. Genet."
    },
    {
      "key": "2023072906401366700_BIB11",
      "doi-asserted-by": "crossref",
      "first-page": "777",
      "DOI": "10.1101/SQB.1993.058.01.085",
      "volume": "58",
      "year": "1993",
      "journal-title": "Cold Spring Harb. Symp. Quant. Biol."
    },
    {
      "key": "2023072906401366700_BIB12"
    },
    {
      "key": "2023072906401366700_BIB13",
      "doi-asserted-by": "crossref",
      "first-page": "1119",
      "DOI": "10.1083/jcb.145.6.1119",
      "volume": "145",
      "year": "1999",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072906401366700_BIB14",
      "doi-asserted-by": "crossref",
      "first-page": "1427",
      "DOI": "10.1083/jcb.135.6.1427",
      "volume": "135",
      "year": "1996",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072906401366700_BIB15",
      "doi-asserted-by": "crossref",
      "first-page": "737",
      "DOI": "10.1172/JCI117028",
      "volume": "93",
      "year": "1994",
      "journal-title": "J. Clin. Invest"
    },
    {
      "key": "2023072906401366700_BIB16",
      "doi-asserted-by": "crossref",
      "first-page": "86",
      "DOI": "10.1016/0962-8924(94)90180-5",
      "volume": "4",
      "year": "1994",
      "journal-title": "Trends Cell Biol."
    },
    {
      "key": "2023072906401366700_BIB17",
      "doi-asserted-by": "crossref",
      "first-page": "1597",
      "DOI": "10.1083/jcb.139.7.1597",
      "volume": "139",
      "year": "1997",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072906401366700_BIB18",
      "doi-asserted-by": "crossref",
      "first-page": "1626",
      "DOI": "10.1002/j.1460-2075.1995.tb07151.x",
      "volume": "14",
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      "journal-title": "EMBO J."
    },
    {
      "key": "2023072906401366700_BIB19",
      "doi-asserted-by": "crossref",
      "first-page": "683",
      "DOI": "10.1016/S0092-8674(04)00171-0",
      "volume": "116",
      "year": "2004",
      "journal-title": "Cell."
    },
    {
      "key": "2023072906401366700_BIB20",
      "doi-asserted-by": "crossref",
      "first-page": "158",
      "DOI": "10.1126/science.1068768",
      "volume": "296",
      "year": "2002",
      "journal-title": "Science."
    },
    {
      "key": "2023072906401366700_BIB21",
      "doi-asserted-by": "crossref",
      "first-page": "358",
      "DOI": "10.1038/331358a0",
      "volume": "331",
      "year": "1988",
      "journal-title": "Nature."
    },
    {
      "key": "2023072906401366700_BIB22",
      "doi-asserted-by": "crossref",
      "first-page": "753",
      "DOI": "10.1083/jcb.200207115",
      "volume": "159",
      "year": "2002",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072906401366700_BIB23",
      "doi-asserted-by": "crossref",
      "first-page": "579",
      "DOI": "10.1083/jcb.200111071",
      "volume": "157",
      "year": "2002",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072906401366700_BIB24",
      "doi-asserted-by": "crossref",
      "first-page": "329",
      "DOI": "10.1038/ng843",
      "volume": "30",
      "year": "2002",
      "journal-title": "Nat. Genet."
    },
    {
      "key": "2023072906401366700_BIB25",
      "doi-asserted-by": "crossref",
      "first-page": "3297",
      "DOI": "10.1242/jcs.114.18.3297",
      "volume": "114",
      "year": "2001",
      "journal-title": "J. Cell Sci."
    },
    {
      "key": "2023072906401366700_BIB26",
      "doi-asserted-by": "crossref",
      "first-page": "1685",
      "DOI": "10.1083/jcb.135.6.1685",
      "volume": "135",
      "year": "1996",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072906401366700_BIB27",
      "doi-asserted-by": "crossref",
      "first-page": "1211",
      "DOI": "10.1083/jcb.146.6.1211",
      "volume": "146",
      "year": "1999",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072906401366700_BIB28",
      "doi-asserted-by": "crossref",
      "first-page": "77",
      "DOI": "10.1023/A:1026799818566",
      "volume": "9",
      "year": "2001",
      "journal-title": "Chromosome Res."
    },
    {
      "key": "2023072906401366700_BIB29",
      "doi-asserted-by": "crossref",
      "first-page": "940",
      "DOI": "10.1101/gad.14.8.940",
      "volume": "14",
      "year": "2000",
      "journal-title": "Genes Dev."
    },
    {
      "key": "2023072906401366700_BIB30",
      "doi-asserted-by": "crossref",
      "first-page": "848",
      "DOI": "10.1038/ni0901-848",
      "volume": "2",
      "year": "2001",
      "journal-title": "Nat. Immunol."
    },
    {
      "key": "2023072906401366700_BIB31",
      "doi-asserted-by": "crossref",
      "first-page": "10",
      "DOI": "10.1006/excr.2002.5513",
      "volume": "276",
      "year": "2002",
      "journal-title": "Exp. Cell Res."
    },
    {
      "key": "2023072906401366700_BIB32",
      "doi-asserted-by": "crossref",
      "first-page": "134",
      "DOI": "10.1038/35055033",
      "volume": "3",
      "year": "2001",
      "journal-title": "Nat. Cell Biol."
    },
    {
      "key": "2023072906401366700_BIB33",
      "doi-asserted-by": "crossref",
      "first-page": "13",
      "DOI": "10.1083/jcb.147.1.13",
      "volume": "147",
      "year": "1999",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072906401366700_BIB34",
      "doi-asserted-by": "crossref",
      "first-page": "1565",
      "DOI": "10.1242/jcs.113.9.1565",
      "volume": "113",
      "year": "2000",
      "journal-title": "J. Cell Sci."
    },
    {
      "key": "2023072906401366700_BIB35",
      "doi-asserted-by": "crossref",
      "first-page": "163",
      "DOI": "10.1006/excr.2001.5400",
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      "year": "2002",
      "journal-title": "Exp. Cell Res."
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    {
      "key": "2023072906401366700_BIB36",
      "first-page": "1168",
      "volume": "16",
      "year": "2002",
      "journal-title": "Mol. Endocrinol."
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    {
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      "first-page": "241",
      "DOI": "10.1007/s004390050686",
      "volume": "102",
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      "journal-title": "Hum. Genet."
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      "first-page": "42",
      "DOI": "10.1016/S1046-2023(02)00289-X",
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    }
  },
  "URL": "http://dx.doi.org/10.1083/jcb.200404107",
  "relation": {},
  "ISSN": [
    "1540-8140",
    "0021-9525"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2004,
        9,
        13
      ]
    ]
  }
}