The Ets transcription factor EHF as a regulator of cornea epithelial cell identity
Authors
Denise N. Stephens, Rachel Herndon Klein, Michael L. Salmans, William Gordon, Hsiang Ho, Bogi Andersen
Institution
UC Irvine
Country
United States
Year
2013
Journal
JBC
Abstract
The cornea is the clear, outer-most portion of
the eye composed of three layers: an epithelium
that provides a protective barrier while
allowing transmission of light into the eye, a
collagen-rich stroma, and an endothelium
monolayer. How cornea development and aging
is controlled is poorly understood. Here we
characterize the mouse cornea transcriptome
from early embryogenesis through aging, and
compare to transcriptomes of other epithelial
tissues, identifying cornea-enriched genes,
pathways, and transcriptional regulators.
Additionally, we profiled corneal epithelium
and stroma, defining genes enriched in these
layers. Over 10,000 genes are differentially
regulated in the mouse cornea across the
timecourse, showing dynamic expression
during development and modest expression
changes in fewer genes during aging. A striking
transition time-point for gene expression
between postnatal days 14 and 28 corresponds
with completion of cornea development at the
transcriptional level. Clustering classifies coexpressed,
and potentially co-regulated, genes
into biologically informative categories,
including groups that exhibit epithelial- or
stromal-enriched expression. Based on these
findings, and through loss of function studies
and ChIP-seq, we show that the Ets
transcription factor EHF promotes cornea
epithelial fate through complementary gene
activating and repressing activities.
Furthermore, we identify potential interactions
between EHF, KLF4, and KLF5 in promoting
corneal epithelial differentiation. These data
provide insights into the mechanisms
underlying epithelial development and aging,
identifying EHF as a regulator of cornea
epithelial identity, and pointing to interactions
between Ets and KLF factors in promoting
epithelial fate. Furthermore, this
comprehensive gene expression dataset for
cornea is a powerful tool for discovery of novel
cornea regulators and pathways.