HMGN Proteins Act in Opposition to ATP-Dependent Chromatin Remodeling Factors to Restrict Nucleosome Mobility

Rattner, Barbara P.; Yusufzai, Timur; Kadonaga, James T.

doi:10.1016/j.molcel.2009.04.014

Cited by 52 publications

(81 citation statements)

References 43 publications

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“…Indeed, nucleosomes bound to either full-length HMGN2 (26) or the NBD (13) are more resistant to thermal denaturation than when in the free state. The staple feature of the NBD suggests that HMGNs may act in opposition to ATP-dependent chromatin remodeling factors by restricting the motion of the DNA in the nucleosome or sterically blocking remodeling factors from binding to the nucleosome (10). Steric interference by HMGNs may also affect the ability of histone modifiers to access and modify their nucleosomal targets (11).…”

Section: Discussionmentioning

confidence: 99%

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Architecture of the high mobility group nucleosomal protein 2-nucleosome complex as revealed by methyl-based NMR

Kato

Ingen

Zhou

et al. 2011

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

166

189

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Chromatin structure and function are regulated by numerous proteins through specific binding to nucleosomes. The structural basis of many of these interactions is unknown, as in the case of the high mobility group nucleosomal (HMGN) protein family that regulates various chromatin functions, including transcription. Here, we report the architecture of the HMGN2-nucleosome complex determined by a combination of methyl-transverse relaxation optimized nuclear magnetic resonance spectroscopy (methyl-TROSY) and mutational analysis. We found that HMGN2 binds to both the acidic patch in the H2A-H2B dimer and to nucleosomal DNA near the entry/exit point, "stapling" the histone core and the DNA. These results provide insight into how HMGNs regulate chromatin structure through interfering with the binding of linker histone H1 to the nucleosome as well as a structural basis of how phosphorylation induces dissociation of HMGNs from chromatin during mitosis. Importantly, our approach is generally applicable to the study of nucleosome-binding interactions in chromatin.

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Section: Discussionmentioning

confidence: 99%

“…HMGNs decompact chromatin condensed by the linker histone H1 (8), thereby enhancing transcription activity of the chromatin template. In addition, HMGNs affect DNA repair (9), chromatin remodeling (10), and the extent of histone modifications (11).…”

mentioning

confidence: 99%

Architecture of the high mobility group nucleosomal protein 2-nucleosome complex as revealed by methyl-based NMR

Kato

Ingen

Zhou

et al. 2011

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

166

189

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“…In the nucleus, HMGN proteins serve as a counterbalance to the action of the many ATP-dependent chromatin remodeling activities which are involved in the formation of actin filaments in the cytoplasm. 5,36) Therefore, we speculated that HMGN2 may be associated with actin filaments. In our studies, we also found that rHMGN2 decreased basal and K. pneumoniae 03183-induced cofilin phosphorylation and inhibited K. pneumoniae 03183-induced actin polymerization.…”

Section: Discussionmentioning

confidence: 99%

“…4) HMGN proteins serve as a counterbalance to the action of the many ATPdependent chromatin remodeling activities in the nucleus. 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.…”

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

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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...

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“…The binding of HMGNs to nucleosomes affects chromatin-related processes such as transcription, replication, and repair (2,4,5,16,20,27,41,43). HMGNs may mediate these effects by causing a change in chromatin structure (5,27) or the level of histone posttranslational modifications (22,23), by affecting ATP-dependent chromatin remodeling activities (30), or by a combination of these.…”

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confidence: 99%

Distinct Properties of Human HMGN5 Reveal a Rapidly Evolving but Functionally Conserved Nucleosome Binding Protein

Malicet

Rochman

Postnikov

et al. 2011

Molecular and Cellular Biology

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The HMGN family is a family of nucleosome-binding architectural proteins that affect the structure and function of chromatin in vertebrates. We report that the HMGN5 variant, encoded by a gene located on chromosome X, is a rapidly evolving protein with an acidic C-terminal domain that differs among vertebrate species. We found that the intranuclear organization and nucleosome interactions of human HMGN5 are distinct from those of mouse HMGN5 and that the C-terminal region of the protein is the main determinant of the chromatin interaction properties. Despite their apparent differences, both mouse and human HMGN5 proteins interact with histone H1, reduce its chromatin residence time, and can induce large-scale chromatin decompaction in living cells. Analysis of HMGN5 mutants suggests that distinct domains in HMGN5 affect specific steps in the interaction of H1 with chromatin. Elevated levels of either human or mouse HMGN5 affect the transcription of numerous genes, most in a variant-specific manner. Our study identifies HMGN5 as a rapidly evolving vertebrate nuclear protein with species-specific properties. HMGN5 has a highly disordered structure, binds dynamically to nucleosome core particles, modulates the binding of H1 to chromatin, reduces the compaction of the chromatin fiber, and affects transcription.

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HMGN Proteins Act in Opposition to ATP-Dependent Chromatin Remodeling Factors to Restrict Nucleosome Mobility

Cited by 52 publications

References 43 publications

Architecture of the high mobility group nucleosomal protein 2-nucleosome complex as revealed by methyl-based NMR

Architecture of the high mobility group nucleosomal protein 2-nucleosome complex as revealed by methyl-based NMR

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

Distinct Properties of Human HMGN5 Reveal a Rapidly Evolving but Functionally Conserved Nucleosome Binding Protein

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