FOXE3 contributes to Peters anomaly through transcriptional regulation of an autophagy-associated protein termed DNAJB1
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 truncate...
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Published in | Nature communications Vol. 7; no. 1; p. 10953 |
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Main Authors | , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
06.04.2016
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
Peter's Anomaly is a developmental disorder of the eye and has been linked to mutations in a range of genes, including the transcription factor FOXE3. Here the authors use next-generation RNA sequencing and mass spectrometry to identify an autophagy-associated protein, DNAJB1 as the transcriptional target of FOXE3. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/ncomms10953 |