A role for chromosomal protein HMGN1 in corneal maturation

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 supra-basal 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.

Conditional Deletion of the Mouse Klf4 Gene Results in Corneal Epithelial Fragility, Stromal Edema, and Loss of Conjunctival Goblet Cells

“…Thus, Klf4 appears to be an integral part of the genetic network that regulates the fine balance between cell proliferation and stratification at the ocular surface. Our re- sults, taken together with other reports, demonstrate that the structural integrity of the corneal epithelium is governed by a complex set of transcription factors, such as KLF4, Pax6, and AP-2␣ (20,23,59,60,72) as well as chromosomal protein HMGN1 (8). It is surprising that in spite of multiple abnormalities associated with the Klf4CN ocular surface in the mouse, the human KLF4 locus has not yet been associated with any ocular dystrophies.…”

The Nucleosome Binding Protein HMGN3 Modulates the Transcription Profile of Pancreatic β Cells and Affects Insulin Secretion

“…1C) and ubiquitously detected in most tissues (6). Furthermore, while the expression of HMGN1 and HMGN2 is generally downregulated during differentiation (4,13,18), our preliminary analyses indicate that HMGN3 protein is first expressed in a few pancreatic cells only after embryonic day 14.5 and the levels of the protein increase during differentiation (data not shown). HMGN3 is highly expressed in the terminally differentiated ␤ cells of both mice and humans.…”

HMGN1 Modulates Estrogen-Mediated Transcriptional Activation through Interactions with Specific DNA-Binding Transcription Factors

“…The overexpression experiments afforded the opportunity to test the mutant HMGN1 proteins for their abilities to impact es- (56,58). Furthermore, this mutant is unable to rescue a number of phenotypes associated with hmgn1 Ϫ/Ϫ mouse embryonic fibroblasts (MEFs) (6,7,42,43,63), a finding which previously suggested that the two substitution mutations abolish the biological activity of HMGN1. Unexpectedly therefore, the effect of the HMGN1 S20E/S24E mutant upon estrogen stimulation differed depending on the target gene.…”

“…on March 21, 2019 by guest http://mcb.asm.org/ esis (6), development (8,35,48), and differentiation, in which its level is tightly regulated and progressively diminished (4,7,33,39,50,52,53). Its effect on estrogen-mediated transcriptional regulation suggests that HMGN may also be involved in the in vivo physiology of estrogen action, which requires further exploration.…”