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FOXE3 contributes to Peters anomaly through transcriptional regulation of an autophagy-associated protein termed DNAJB1

Author

Listed:
  • Shahid Y. Khan

    (The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA)

  • Shivakumar Vasanth

    (The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA)

  • Firoz Kabir

    (The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA)

  • John D. Gottsch

    (The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA)

  • Arif O. Khan

    (King Khaled Eye Specialist Hospital)

  • Raghothama Chaerkady

    (Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, Maryland 21205, USA)

  • Mei-Chong W. Lee

    (University of California)

  • Carmen C. Leitch

    (Diabetes, and Nutrition, University of Maryland School of Medicine, 660 West Redwood Street, Baltimore, Maryland 21201, USA)

  • Zhiwei Ma

    (Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health)

  • Julie Laux

    (Laboratory of Immunology, National Eye Institute, National Institutes of Health)

  • Rafael Villasmil

    (Laboratory of Immunology, National Eye Institute, National Institutes of Health)

  • Shaheen N. Khan

    (National Centre of Excellence in Molecular Biology, University of the Punjab)

  • Sheikh Riazuddin

    (National Centre of Excellence in Molecular Biology, University of the Punjab
    Allama Iqbal Medical College, University of Health Sciences
    National Centre for Genetic Diseases, Shaheed Zulfiqar Ali Bhutto Medical University)

  • Javed Akram

    (Allama Iqbal Medical College, University of Health Sciences
    National Centre for Genetic Diseases, Shaheed Zulfiqar Ali Bhutto Medical University)

  • Robert N. Cole

    (Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, Maryland 21205, USA)

  • C. Conover Talbot

    (Institute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, Maryland 21205, USA)

  • Nader Pourmand

    (University of California)

  • Norann A. Zaghloul

    (Diabetes, and Nutrition, University of Maryland School of Medicine, 660 West Redwood Street, Baltimore, Maryland 21201, USA)

  • J. Fielding Hejtmancik

    (Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health)

  • S. Amer Riazuddin

    (The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA)

Abstract

FOXE3 is a lens-specific transcription factor that has been associated with anterior segment ocular dysgenesis. To determine the transcriptional target(s) of FOXE3 that are indispensable for the anterior segment development, we examined the transcriptome and the proteome of cells expressing truncated FOXE3 responsible for Peters anomaly identified through linkage-coupled next-generation whole-exome sequencing. We found that DNAJB1, an autophagy-associated protein, was the only candidate exhibiting differential expression in both screens. We confirmed the candidacy of DNAJB1 through chromatin immunoprecipitation and luciferase assays while knockdown of DNAJB1 in human lens epithelial cells resulted in a mitotic arrest. Subsequently, we targeted dnajb1a in zebrafish through injection of a splice-blocking morpholino. The dnajb1a morphants exhibited underdeveloped cataractous lenses with persistent apoptotic nuclei. In conclusion, here we report DNAJB1 is a transcriptional target of FOXE3 in a novel pathway that is crucial for the development of the anterior segment of the eye.

Suggested Citation

  • Shahid Y. Khan & Shivakumar Vasanth & Firoz Kabir & John D. Gottsch & Arif O. Khan & Raghothama Chaerkady & Mei-Chong W. Lee & Carmen C. Leitch & Zhiwei Ma & Julie Laux & Rafael Villasmil & Shaheen N., 2016. "FOXE3 contributes to Peters anomaly through transcriptional regulation of an autophagy-associated protein termed DNAJB1," Nature Communications, Nature, vol. 7(1), pages 1-15, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10953
    DOI: 10.1038/ncomms10953
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