The effect of linker histones nucleosome binding affinity on chromatin unfolding mechanisms

Rosana Collepardo-Guevara, Tamar Schlick

Research output: Contribution to journalArticle

Abstract

Eukaryotic gene activation requires selective unfolding of the chromatin fiber to access the DNA for processes such as DNA transcription, replication, and repair. Mutation/modification experiments of linker histone (LH) H1 suggest the importance of dynamic mechanisms for LH binding/dissociation, but the effects on chromatins unfolding pathway remain unclear. Here we investigate the stretching response of chromatin fibers by mesoscale modeling to complement single-molecule experiments, and present various unfolding mechanisms for fibers with different nucleosome repeat lengths (NRLs) with/without LH that are fixed to their cores or bind/unbind dynamically with different affinities. Fiber softening occurs for long compared to short NRL (due to facile stacking rearrangements), dynamic compared to static LH/core binding as well as slow rather than fast dynamic LH rebinding (due to DNA stem destabilization), and low compared to high LH concentration (due to DNA stem inhibition). Heterogeneous superbead constructs - nucleosome clusters interspersed with extended fiber regions - emerge during unfolding of medium-NRL fibers and may be related to those observed experimentally. Our work suggests that fast and slow LH binding pools, present simultaneously in vivo, might act cooperatively to yield controlled fiber unfolding at low forces. Medium-NRL fibers with multiple dynamic LH pools offer both flexibility and selective DNA exposure, and may be evolutionarily suitable to regulate chromatin architecture and gene expression.

Original languageEnglish (US)
Pages (from-to)1670-1680
Number of pages11
JournalBiophysical Journal
Volume101
Issue number7
DOIs
StatePublished - Oct 5 2011

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Nucleosomes
Histones
Chromatin
DNA
DNA Replication
DNA Repair
Transcriptional Activation
Gene Expression
Mutation

ASJC Scopus subject areas

  • Biophysics

Cite this

The effect of linker histones nucleosome binding affinity on chromatin unfolding mechanisms. / Collepardo-Guevara, Rosana; Schlick, Tamar.

In: Biophysical Journal, Vol. 101, No. 7, 05.10.2011, p. 1670-1680.

Research output: Contribution to journalArticle

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