Chromatin-associated HMG-17 is a major regulator of homeodomain transcription factor activity modulated by Wnt/ -catenin signaling

Amen, Melanie; Espinoza, Herbert M.; Cox, Carol J.; Liang, Xiaowen; Wang, Jianbo; Link, Todd; Brennan, Richard G.; Martin, James F.; Amendt, Brad A.

doi:10.1093/nar/gkm1047

Cited by 42 publications

(69 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HMG-17 forms a chromatin complex with PITX2 to repress PITX2 transcriptional activity. This complex is inactive and switched to an active transcriptional complex through the interaction of ␤-catenin with PITX2 (49).…”

Section: Discussionmentioning

confidence: 99%

Chromatin protein HMGB2 regulates articular cartilage surface maintenance via β-catenin pathway

Taniguchi

Caramés

Kawakami

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The superficial zone (SZ) of articular cartilage is critical in maintaining tissue function and homeostasis and represents the site of the earliest changes in osteoarthritis. Mechanisms that regulate the unique phenotype of SZ chondrocytes and maintain SZ integrity are unknown. We recently demonstrated that expression of the chromatin protein high mobility group box (HMGB) protein 2 is restricted to the SZ in articular cartilage suggesting a transcriptional regulation involving HMGB2 in SZ. Here, we show that an interaction between HMGB2 and the Wnt/␤-catenin pathway regulates the maintenance of the SZ. We found that the Wnt/␤-catenin pathway is active specifically in the SZ in normal mouse knee joints and colocalizes with HMGB2. Both Wnt signaling and HMGB2 expression decrease with aging in mouse joints. Our molecular studies show that HMGB2 enhances the binding of Lef-1 to its target sequence and potentiates transcriptional activation of the Lef-1-␤-catenin complex. The HMG domain within HMGB2 is crucial for interaction with Lef-1, suggesting that both HMGB2 and HMGB1 may be involved in this function. Furthermore, conditional deletion of ␤-catenin in cultured mouse chondrocytes induced apoptosis. These findings define a pathway where protein interactions of HMGB2 and Lef-1 enhance Wnt signaling and promote SZ chondrocyte survival. Loss of the HMGB2-Wnt signaling interaction is a new mechanism in aging-related cartilage pathology.aging ͉ osteoarthritis ͉ apoptosis ͉ superficial zone A rticular cartilage is a tissue that provides biomechanical properties that allow near frictionless joint movement and dispersion of mechanical loads. Cartilage is composed of a single cell lineage but differences in the organization, phenotype and function of cells in the various layers of cartilage have been recognized (1-4). The superficial zone (SZ) is the most unique. SZ cells produce lubricin, also termed proteoglycan-4 (PRG4) or superficial zone protein (SZP), an important joint lubricant (5-7), and are more responsive to stimulation by catabolic cytokines such as IL-1 (8). Recent studies also suggest that the SZ contains cells that express mesenchymal stem cell markers (9-11).Articular cartilage is among the tissues that undergo profound aging-related changes and aging represents the major risk factor for osteoarthritis (OA), the most prevalent joint disease (12). Agingrelated changes in cartilage include reduced cellularity, increased apoptosis and altered cellular responses to growth factors, cytokines and mechanical stress (13-15). Cartilage changes in aging and OA begin in the SZ and once the SZ is disrupted this is followed by progressive erosion of the remaining cartilage layers (16).To address mechanisms that maintain the unique phenotype of SZ cells we performed gene expression analyses and observed that expression of the chromatin protein HMGB2 is restricted to the SZ (17). Joint aging in humans and mice leads to loss of HMGB2 expression and this is correlated with the onset of OA-like changes. Mice deficient in Hm...

show abstract

Section: Discussionmentioning

confidence: 99%

Chromatin protein HMGB2 regulates articular cartilage surface maintenance via β-catenin pathway

Taniguchi

Caramés

Kawakami

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…HMGN2 is present in most vertebrate cells and functions as an architectural element to alter the structure of chromatin fiber and enhance transcription from the chromatin template (7). HMGN2 facilitates the ability of DNA repair proteins to access and repair UV-induced DNA lesions in chromatin (8), and is a regulator of homeodomain transcription factor activity modulated by Wnt/␤-catenin signaling (9). HMGN2 has broad spectrum antimicrobial activity against bacteria (10) and promotes lipopolysaccharide (LPS)-induced ␤-defensin expression in epithelial cells (11).…”

Section: High Mobility Group Nucleosomal Binding Domain 2 (Hmgn2)mentioning

confidence: 99%

“…HMGN2 is a ubiquitous non-histone chromosomal protein that plays a role as an architectural element to alter the structure of the chromatic fiber and regulate transcriptional activity (7,9). Recently, phosphorylation and acetylation have been known as post-translational modifications of HMGN2 protein that influence the binding of HMGN2 to nucleosomes (27).…”

Section: Hmgn2 Is Sumoylated In An E Coli Over-expression System-mentioning

confidence: 99%

High Mobility Group Nucleosomal Binding Domain 2 (HMGN2) SUMOylation by the SUMO E3 Ligase PIAS1 Decreases the Binding Affinity to Nucleosome Core Particles

Kim²,

Kwak³

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: HMGN2 is an important nuclear protein that is involved in altering the chromatin structure and facilitating the transcriptional activation. Results: HMGN2 is modified by SUMO1 with help of E3 ligase PIAS1. Conclusion: HMGN2-SUMOylation is a significant factor in the regulation of chromatin structure and function. Significance: Our finding is the identification of the new modification of HMGN2.

show abstract

“…5) HMGN2 is a major regulator of homeodomain transcription factor activity modulated by Wnt/beta-catenin signaling. 6) Recently, an additional role for HMGN2 outside the cell nucleus has come into focus. HMGN2 shows potent antimicrobial activity against Escherichia coli ML-35p, Pseudomonas aeruginosa ATCC 27853 and, to some extent, against Candida albicans ATCC 10231.…”

mentioning

confidence: 99%

High Mobility Group Nucleosomal Binding Domain 2 Protein Protects Bladder Epithelial Cells from Klebsiella pneumoniae Invasion

Cao

Fan

et al. 2011

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Due to the predominance of multiple-antibiotic-resistant Klebsiella pneumoniae strains, the search for new approaches for the prevention of K. pneumoniae infections is now under intensive investigation. The objective of the present study was to investigate the effects of high mobility group nucleosomal binding domain 2 (HMGN2) protein, which acts on the bladder epithelial cells T 24, on the invasion of K. pneumoniae 03183 and explore its possible mechanisms. Pretreatment with HMGN2 significantly reduced K. pneumoniae 03183 uptake by T 24 cells. In T 24 cells, there were no detectable cytotoxic effects of HMGN2 at any concentration between 32 and 256 m mg/ml after 2 h incubation. HMGN2 exhibited no appreciable antibacterial activity against K. pneumoniae 03183. Fluorescence microscopy and flow cytometry analysis revealed that HMGN2 blocked K. pneumoniae 03183-induced actin polymerization. K. pneumoniae 03183-induced phosphorylation of extracellular signal-regulated kinase (ERK) and cofilin were prevented by pretreatment with HMGN2. These results indicated that pretreatment with HMGN2 inhibited cofilin phosphorylation and then induced actin disruption which may block ERK phosphorylation. These changes led to inhibition of K. pneumoniae 03183 invasion of T 24 bladder epithelial cells.Key words high mobility group nucleosomal binding domain 2; actin; Klebsiella pneumoniae; extracellular signal-regulated kinase; cofilin Biol. Pharm. Bull. 34(7) 1065-1071 (2011) © 2011 Pharmaceutical Society of Japan * To whom correspondence should be addressed. e-mail: huangpanxiaoxiao@sina.com tein Assay Kit (Pierce, U.S.A.) and the purity was confirmed by Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting with a primary antibody mouse anti-His monoclonal antibody (Roche, U.K.).Invasion Assay For the invasion assay, T 24 cells were seeded at 5ϫ10 4 cells per well in 24-well plates. Cells were preincubated with substances (rHMGN2 or cytochalasin B or latrunculin B or Y27632 or PD98059) for 2 h prior to bacterial infection in order to study the cell structures and processes involved in internalization. The monolayers were washed twice with PBS to remove any substances prior to infection with K. pneumoniae 03183. In each well of a 24-well cell culture cluster, about 5ϫ10 6 mid-log-phase K. pneumoniae 03183 (OD 600 ϭ0.4-0.6) were added to epithelial cells per well. Invasion was allowed to occur for 2 h at 37°C in 5% CO 2 . Before a second 2 h incubation (kill) period under the same conditions but with fresh medium containing 100 mg of gentamicin per ml, monolayers were washed once with PBS (pH 7.4). During the kill period, all extracellular K. pneumoniae 03183 were killed but the viability of internalized bacteria was not affected. Finally, monolayers were washed twice with PBS and lysed with 0.1% Triton X-100 and the released intracellular bacteria were enumerated by plate count. The number of intracellular K. pneumoniae 03183 after invasion in the presence of an inhibitor was divided b...

show abstract

Chromatin-associated HMG-17 is a major regulator of homeodomain transcription factor activity modulated by Wnt/ -catenin signaling

Cited by 42 publications

References 41 publications

Chromatin protein HMGB2 regulates articular cartilage surface maintenance via β-catenin pathway

Chromatin protein HMGB2 regulates articular cartilage surface maintenance via β-catenin pathway

High Mobility Group Nucleosomal Binding Domain 2 (HMGN2) SUMOylation by the SUMO E3 Ligase PIAS1 Decreases the Binding Affinity to Nucleosome Core Particles

High Mobility Group Nucleosomal Binding Domain 2 Protein Protects Bladder Epithelial Cells from Klebsiella pneumoniae Invasion

Contact Info

Product

Resources

About