Binding of Histone H1 to DNA Is Differentially Modulated by Redox State of HMGB1

Eva Polanská,Šárka Pospíšilová,Michal Štros,Yamini Dalal

doi:10.1371/journal.pone.0089070

Eva Polanská, Šárka Pospíšilová + Show 2 more

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https://doi.org/10.1371/journal.pone.0089070

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Abstract

HMGB1 is an architectural protein in chromatin, acting also as a signaling molecule outside the cell. Recent reports from several laboratories provided evidence that a number of both the intracellular and extracellular functions of HMGB1 may depend on redox-sensitive cysteine residues of the protein. In this study we demonstrate that redox state of HMGB1 can significantly modulate the ability of the protein to bind and bend DNA, as well as to promote DNA end-joining. We also report a high affinity binding of histone H1 to hemicatenated DNA loops and DNA minicircles. Finally, we show that reduced HMGB1 can readily displace histone H1 from DNA, while oxidized HMGB1 has limited capacity for H1 displacement. Our results suggested a novel mechanism for the HMGB1-mediated modulation of histone H1 binding to DNA. Possible biological consequences of linker histones H1 replacement by HMGB1 for the functioning of chromatin are discussed.

Highlights

Chromatin-associated protein HMGB1 has been implicated in DNA replication, recombination, repair and transcription, as well as in cell signaling, promotion of tumor growth and metastasis
Redox State-dependent Modulation of DNA Bending and DNA End-joining by HMGB1 Reports from several laboratories provided evidence that both intracellular and extracellular functions of HMGB1 may depend on redox-sensitive cysteine residues of the protein (Cys23, Cys45 and Cys106, reviewed in [2])
To find out the impact of the redox-state of HMGB1 on binding of the protein to other DNA structure, we have studied binding of reduced and oxidized HMGB1 to hemicatenated DNA loops. hcDNA was originally discovered by Gaillard and Strauss [25] by re-association of the strands of a DNA fragment containing a track of repetitive poly(CA).poly(TG) sequence from CA-microsatellite

Summary

Introduction

Chromatin-associated protein HMGB1 has been implicated in DNA replication, recombination, repair and transcription, as well as in cell signaling, promotion of tumor growth and metastasis (reviewed in [1]). HMGB1 can act as an extracellular damage associated molecular pattern molecule (DAMP), regulating cell death and survival [2,3]. Recent reports from several laboratories provided evidence that both intracellular and extracellular functions of HMGB1 may depend on redox-sensitive cysteine residues of the protein (reviewed in [2]). It has been shown that redox state (oxidation or modification of cysteine residues) of HMGB1 could impair the binding affinity of the protein to linear cisplatin-modified DNA or superhelical DNA [7,8,9,10]

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