PUBLICATION
FOXE3 contributes to Peters anomaly through transcriptional regulation of an autophagy-associated protein termed DNAJB1
- Authors
- Khan, S.Y., Vasanth, S., Kabir, F., Gottsch, J.D., Khan, A.O., Chaerkady, R., Lee, M.W., Leitch, C.C., Ma, Z., Laux, J., Villasmil, R., Khan, S.N., Riazuddin, S., Akram, J., Cole, R.N., Talbot, C.C., Pourmand, N., Zaghloul, N.A., Hejtmancik, J.F., Riazuddin, S.A.
- ID
- ZDB-PUB-160525-6
- Date
- 2016
- Source
- Nature communications 7: 10953 (Journal)
- Registered Authors
- Hejtmancik, J. Fielding, Zaghloul, Norann A.
- Keywords
- Biological sciences, Genetics, Molecular biology
- MeSH Terms
-
- Pedigree
- Gene Knockdown Techniques
- Eye Abnormalities/genetics*
- Eye Abnormalities/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- Forkhead Transcription Factors/genetics*
- Forkhead Transcription Factors/metabolism
- HEK293 Cells
- Male
- Autophagy/genetics*
- Gene Expression Profiling/methods
- Family Health
- Female
- Lens, Crystalline/pathology
- HSP40 Heat-Shock Proteins/genetics*
- HSP40 Heat-Shock Proteins/metabolism
- Corneal Opacity/genetics*
- Corneal Opacity/metabolism
- Exome Sequencing/methods
- Epithelial Cells/metabolism
- Epithelial Cells/pathology
- Gene Expression Regulation*
- Humans
- Animals
- PubMed
- 27218149 Full text @ Nat. Commun.
Citation
Khan, S.Y., Vasanth, S., Kabir, F., Gottsch, J.D., Khan, A.O., Chaerkady, R., Lee, M.W., Leitch, C.C., Ma, Z., Laux, J., Villasmil, R., Khan, S.N., Riazuddin, S., Akram, J., Cole, R.N., Talbot, C.C., Pourmand, N., Zaghloul, N.A., Hejtmancik, J.F., Riazuddin, S.A. (2016) FOXE3 contributes to Peters anomaly through transcriptional regulation of an autophagy-associated protein termed DNAJB1. Nature communications. 7:10953.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping