A role for chromosomal protein HMGN1 in corneal maturation

Yehudit Birger, Janine Davis, Takashi Furusawa, Eyal Rand, Joram Piatigorsky*, Michael Bustin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Corneal differentiation and maturation are associated with major changes in the expression levels of numerous genes, including those coding for the chromatin-binding high-mobility group (HMG) proteins. Here we report that HMGN1, a nucleosome-binding protein that alters the structure and activity of chromatin, affects the development of the corneal epithelium in mice. The corneal epithelium of Hmgn1-/- mice is thin, has a reduced number of cells, is poorly stratified, is depleted of suprabasal wing cells, and its most superficial cell layer blisters. In mature Hmgn1-/-mice, the basal cells retain the ovoid shape of immature cells, and rest directly on the basal membrane which is disorganized. Gene expression was modified in Hmgn1 -/- corneas: glutathione-S-transferase (GST)α 4and GST ω 1, epithelial layer-specific markers, were selectively reduced while E-cadherin and α-, β-, and γ-catenin, components of adherens junctions, were increased. Immunofluorescence analysis reveals a complete co-localization of HMGN1 and p63 in small clusters of basal corneal epithelial cells of wild-type mice, and an absence of p63 expressing cells in the central region of the Hmgn1-/- cornea. We suggest that interaction of HMGN1 with chromatin modulates the fidelity of gene expression and affects corneal development and maturation.

Original languageEnglish
Pages (from-to)19-29
Number of pages11
JournalDifferentiation
Volume74
Issue number1
DOIs
StatePublished - Feb 2006
Externally publishedYes

Funding

FundersFunder number
National Institutes of Health
National Eye Institute
National Cancer InstituteZ01BC004496

    Keywords

    • Chromatin
    • Corneal epithelium
    • Eye differentiation
    • HMG proteins

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