DOI: 10.1073/pnas.93.24.13943. NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development

NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development

10.1073/pnas.93.24.13943

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The locus control region of the β-globin gene is composed of four erythroid-specific hypersensitive sites. Hypersensitive site 2 has been shown to be a powerful enhancer and contains a tandem repeat sequence for the transcription factors AP1 and NFE2 (activating protein 1 and nuclear factor erythroid 2, respectively). The human NRF2 (NFE2 related factor 2) has been isolated by bacterial expression screening using this core sequence as a probe. p45-NFE2, NRF1, and NRF2 belong to the CNC (“cap ‘n’ collar”) subfamily of the basic region–leucine zipper transcription factors, which exhibits strong homology at specific regions such as the “CNC” and the DNA binding and leucine zipper domains. Although the erythroid-specific p45-NFE2 has been implicated in globin gene regulation, p45-NFE2 null mice succumb to bleedings due to lack of platelets and those that survive exhibit only a mild anemia. To determine the function of NRF2, which we found to be widely expressed in vivo , we have characterized the genomic structure of the mouse NRF2 gene, disrupted the Nrf2 gene by homologous recombination in mouse embryonic stem cells (ES cells), and generated NRF2 −/− mice. Homozygous mutant mice developed normally, were not anemic, reached adulthood, and reproduced. Our studies indicate that NRF2 is dispensable for mouse development.

Bibliography

Chan, K., Lu, R., Chang, J. C., & Kan, Y. W. (1996). NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, andâdevelopment. Proceedings of the National Academy of Sciences, 93(24), 13943â13948.

Authors 4

Kaimin Chan (first)
Ronghua Lu (additional)
Judy C. Chang (additional)
Yuet Wai Kan (additional)

References 33 Referenced 562

10.1073/pnas.82.19.6384
10.1073/pnas.83.5.1359
10.1093/nar/15.24.10159
10.1016/0092-8674(87)90584-8
10.1073/pnas.86.18.7082
10.1073/pnas.86.18.7033
10.1101/gad.3.3.314
10.1038/344309a0
10.1073/pnas.89.9.3899
10.1073/pnas.87.22.9000
10.1073/pnas.88.22.10188
10.1101/gad.4.6.993
10.1002/j.1460-2075.1990.tb08100.x
10.1073/pnas.89.7.3107
10.1016/0925-4773(91)90086-L
10.1038/362722a0
10.1073/pnas.90.24.11488
10.1073/pnas.90.23.11371
10.1073/pnas.91.21.9926
10.1093/nar/22.12.2383
10.1007/BF00225191
10.1038/367568a0
10.1016/0092-8674(95)90531-6
10.1073/pnas.92.19.8690
10.1073/pnas.93.8.3514
10.1016/0092-8674(87)90646-5
L M Angerer, R C Angerer In Situ Hybridization: A Practical Approach, ed D G Wilkinson (IRL, Oxford), pp. 15–32 (1992). / In Situ Hybridization: A Practical Approach by Angerer L M (1992)
10.1016/0092-8674(91)90011-M
10.1073/pnas.84.15.5316
J Sambrook, E F Fritsh, T Maniatis Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. Press, 2nd Ed., Plainview, NY, 1989). / Molecular Cloning: A Laboratory Manual by Sambrook J (1989)
10.1006/bbrc.1995.1467
10.1073/pnas.91.18.8398
10.1128/MCB.15.8.4184

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 6:35 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 11:05 a.m.)
Indexed	1 month ago (Aug. 5, 2025, 8:37 a.m.)
Issued	28 years, 9 months ago (Nov. 26, 1996)
Published	28 years, 9 months ago (Nov. 26, 1996)
Published Online	28 years, 9 months ago (Nov. 26, 1996)
Published Print	28 years, 9 months ago (Nov. 26, 1996)

Funders 0

None

BibTeX

@article{Chan_1996, title={NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development}, volume={93}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.93.24.13943}, DOI={10.1073/pnas.93.24.13943}, number={24}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Chan, Kaimin and Lu, Ronghua and Chang, Judy C. and Kan, Yuet Wai}, year={1996}, month=nov, pages={13943–13948} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        5
      ]
    ],
    "date-time": "2025-08-05T12:37:35Z",
    "timestamp": 1754397455965
  },
  "reference-count": 33,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "24",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        1996,
        11,
        26
      ]
    ]
  },
  "abstract": "<jats:p>\n            The locus control region of the \u03b2-globin gene is composed of four\n erythroid-specific hypersensitive sites. Hypersensitive site 2 has been\n shown to be a powerful enhancer and contains a tandem repeat sequence\n for the transcription factors AP1 and NFE2 (activating protein 1 and\n nuclear factor erythroid 2, respectively). The human NRF2 (NFE2 related\n factor 2) has been isolated by bacterial expression screening using\n this core sequence as a probe. p45-NFE2, NRF1, and NRF2 belong to the\n CNC (\u201ccap \u2018n\u2019 collar\u201d) subfamily of the basic region\u2013leucine\n zipper transcription factors, which exhibits strong homology at\n specific regions such as the \u201cCNC\u201d and the DNA binding and\n leucine zipper domains. Although the erythroid-specific p45-NFE2 has\n been implicated in globin gene regulation, p45-NFE2 null mice succumb\n to bleedings due to lack of platelets and those that survive exhibit\n only a mild anemia. To determine the function of NRF2, which we found\n to be widely expressed\n            <jats:italic>in vivo</jats:italic>\n            , we have characterized\n the genomic structure of the mouse NRF2 gene, disrupted the Nrf2 gene\n by homologous recombination in mouse embryonic stem cells (ES cells),\n and generated NRF2\n            <jats:sup>\u2212/\u2212</jats:sup>\n            mice. Homozygous mutant mice\n developed normally, were not anemic, reached adulthood, and reproduced.\n Our studies indicate that NRF2 is dispensable for mouse development.\n          </jats:p>",
  "DOI": "10.1073/pnas.93.24.13943",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        26
      ]
    ],
    "date-time": "2002-07-26T10:35:50Z",
    "timestamp": 1027679750000
  },
  "page": "13943-13948",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 562,
  "title": "NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and\u2009development",
  "prefix": "10.1073",
  "volume": "93",
  "author": [
    {
      "given": "Kaimin",
      "family": "Chan",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Institute of Molecular Biology, University of Hong Kong, 6 Sassoon\r Road, Hong Kong; and Department of Laboratory Medicine, and\r Howard Hughes Medical Institute and Cardiovascular Research\r Institute, University of California, San Francisco, CA 94143-0724"
        }
      ]
    },
    {
      "given": "Ronghua",
      "family": "Lu",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Institute of Molecular Biology, University of Hong Kong, 6 Sassoon\r Road, Hong Kong; and Department of Laboratory Medicine, and\r Howard Hughes Medical Institute and Cardiovascular Research\r Institute, University of California, San Francisco, CA 94143-0724"
        }
      ]
    },
    {
      "given": "Judy\u2009C.",
      "family": "Chang",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Institute of Molecular Biology, University of Hong Kong, 6 Sassoon\r Road, Hong Kong; and Department of Laboratory Medicine, and\r Howard Hughes Medical Institute and Cardiovascular Research\r Institute, University of California, San Francisco, CA 94143-0724"
        }
      ]
    },
    {
      "given": "Yuet\u2009Wai",
      "family": "Kan",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Institute of Molecular Biology, University of Hong Kong, 6 Sassoon\r Road, Hong Kong; and Department of Laboratory Medicine, and\r Howard Hughes Medical Institute and Cardiovascular Research\r Institute, University of California, San Francisco, CA 94143-0724"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        1996,
        11,
        26
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_2_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.82.19.6384"
    },
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.83.5.1359"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/15.24.10159"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(87)90584-8"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.86.18.7082"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.86.18.7033"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.3.3.314"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/344309a0"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.89.9.3899"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.87.22.9000"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.88.22.10188"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.4.6.993"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1990.tb08100.x"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.89.7.3107"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0925-4773(91)90086-L"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/362722a0"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.90.24.11488"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.90.23.11371"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.91.21.9926"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/22.12.2383"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF00225191"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/367568a0"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(95)90531-6"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.92.19.8690"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.93.8.3514"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(87)90646-5"
    },
    {
      "key": "e_1_3_2_27_2",
      "first-page": "15",
      "volume-title": "In Situ Hybridization: A Practical Approach",
      "author": "Angerer L M",
      "year": "1992",
      "unstructured": "L M Angerer, R C Angerer In Situ Hybridization: A Practical Approach, ed D G Wilkinson (IRL, Oxford), pp. 15\u201332 (1992)."
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(91)90011-M"
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.84.15.5316"
    },
    {
      "key": "e_1_3_2_30_2",
      "volume-title": "Molecular Cloning: A Laboratory Manual",
      "author": "Sambrook J",
      "year": "1989",
      "unstructured": "J Sambrook, E F Fritsh, T Maniatis Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. Press, 2nd Ed., Plainview, NY, 1989).",
      "edition": "2"
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/bbrc.1995.1467"
    },
    {
      "key": "e_1_3_2_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.91.18.8398"
    },
    {
      "key": "e_1_3_2_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.15.8.4184"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.93.24.13943",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        4,
        13
      ]
    ],
    "date-time": "2022-04-13T15:05:32Z",
    "timestamp": 1649862332000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.93.24.13943"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1996,
        11,
        26
      ]
    ]
  },
  "references-count": 33,
  "journal-issue": {
    "issue": "24",
    "published-print": {
      "date-parts": [
        [
          1996,
          11,
          26
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.93.24.13943"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.93.24.13943",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        1996,
        11,
        26
      ]
    ]
  },
  "assertion": [
    {
      "value": "1996-08-23",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "1996-11-26",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}