Single and double box HMGB proteins differentially destabilize nucleosomes

Micah J. McCauley, Ran Huo, Nicole Becker, Molly Nelson Holte, Uma M. Muthurajan, Ioulia Rouzina, Karolin Luger, L James Maher III, Nathan E. Israeloff, Mark C. Williams

Research output: Contribution to journalArticle

Abstract

Nucleosome disruption plays a key role in many nuclear processes including transcription, DNA repair and recombination. Here we combine atomic force microscopy (AFM) and optical tweezers (OT) experiments to show that high mobility group B (HMGB) proteins strongly disrupt nucleosomes, revealing a new mechanism for regulation of chromatin accessibility. We find that both the double box yeast Hmo1 and the single box yeast Nhp6A display strong binding preferences for nucleosomes over linker DNA, and both HMGB proteins destabilize and unwind DNA from the H2A-H2B dimers. However, unlike Nhp6A, Hmo1 also releases half of the DNA held by the (H3-H4)2 tetramer. This difference in nucleosome destabilization may explain why Nhp6A and Hmo1 function at different genomic sites. Hmo1 is enriched at highly transcribed ribosomal genes, known to be depleted of histones. In contrast, Nhp6A is found across euchromatin, pointing to a significant difference in cellular function.

Original languageEnglish (US)
Pages (from-to)666-678
Number of pages13
JournalNucleic Acids Research
Volume47
Issue number2
DOIs
StatePublished - Jan 25 2019

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HMGB Proteins
Nucleosomes
High Mobility Group Proteins
DNA
Yeasts
Optical Tweezers
Euchromatin
Atomic Force Microscopy
DNA Repair
Histones
Genetic Recombination
Chromatin
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

McCauley, M. J., Huo, R., Becker, N., Holte, M. N., Muthurajan, U. M., Rouzina, I., ... Williams, M. C. (2019). Single and double box HMGB proteins differentially destabilize nucleosomes. Nucleic Acids Research, 47(2), 666-678. https://doi.org/10.1093/nar/gky1119

Single and double box HMGB proteins differentially destabilize nucleosomes. / McCauley, Micah J.; Huo, Ran; Becker, Nicole; Holte, Molly Nelson; Muthurajan, Uma M.; Rouzina, Ioulia; Luger, Karolin; Maher III, L James; Israeloff, Nathan E.; Williams, Mark C.

In: Nucleic Acids Research, Vol. 47, No. 2, 25.01.2019, p. 666-678.

Research output: Contribution to journalArticle

McCauley, MJ, Huo, R, Becker, N, Holte, MN, Muthurajan, UM, Rouzina, I, Luger, K, Maher III, LJ, Israeloff, NE & Williams, MC 2019, 'Single and double box HMGB proteins differentially destabilize nucleosomes', Nucleic Acids Research, vol. 47, no. 2, pp. 666-678. https://doi.org/10.1093/nar/gky1119
McCauley MJ, Huo R, Becker N, Holte MN, Muthurajan UM, Rouzina I et al. Single and double box HMGB proteins differentially destabilize nucleosomes. Nucleic Acids Research. 2019 Jan 25;47(2):666-678. https://doi.org/10.1093/nar/gky1119
McCauley, Micah J. ; Huo, Ran ; Becker, Nicole ; Holte, Molly Nelson ; Muthurajan, Uma M. ; Rouzina, Ioulia ; Luger, Karolin ; Maher III, L James ; Israeloff, Nathan E. ; Williams, Mark C. / Single and double box HMGB proteins differentially destabilize nucleosomes. In: Nucleic Acids Research. 2019 ; Vol. 47, No. 2. pp. 666-678.
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