title: Dynamic condensation of linker histone C-terminal domain regulates chromatin structure.
abstract: The basic and intrinsically disordered C-terminal domain (CTD) of the linker histone (LH) is essential for chromatin compaction. However, its conformation upon nucleosome binding and its impact on chromatin organization remain unknown. Our mesoscale chromatin model with a flexible LH CTD captures a dynamic, salt-dependent condensation mechanism driven by charge neutralization between the LH and linker DNA. Namely, at low salt concentration, CTD condenses, but LH only interacts with the nucleosome and one linker DNA, resulting in a semi-open nucleosome configuration; at higher salt, LH interacts with the nucleosome and two linker DNAs, promoting stem formation and chromatin compaction. CTD charge reduction unfolds the domain and decondenses chromatin, a mechanism in consonance with reduced counterion screening in vitro and phosphorylated LH in vivo. Divalent ions counteract this decondensation effect by maintaining nucleosome stems and expelling the CTDs to the fiber exterior. Additionally, we explain that the CTD folding depends on the chromatin fiber size, and we show that the asymmetric structure of the LH globular head is responsible for the uneven interaction observed between the LH and the linker DNAs. All these mechanisms may impact epigenetic regulation and higher levels of chromatin folding.
authors.affiliation: Department of Chemistry, New York University, 100 Washington Square East, New York, NY 10003, USA.
authors.forename: Antoni
authors.initials: A
authors.lastname: Luque
authors.affiliation: University of Cambridge, Department of Chemistry, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Rosana
authors.initials: R
authors.lastname: Collepardo-Guevara
authors.affiliation: Department of Biochemistry and Molecular Biology, Penn State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Sergei
authors.initials: S
authors.lastname: Grigoryev
authors.affiliation: Department of Chemistry, New York University, 100 Washington Square East, New York, NY 10003, USA Courant Institute of Mathematical Sciences, New York University, 251 Mercer Street, New York, NY 10012, USA schlick@nyu.edu.
authors.forename: Tamar
authors.initials: T
authors.lastname: Schlick
mesh_terms: D002843:Chromatin / Q000737:chemistry*; D006657:Histones / Q000737:chemistry*; D008274:Magnesium / Q000737:chemistry; D008958:Models, Molecular; D009707:Nucleosomes / Q000737:chemistry; D017434:Protein Structure, Tertiary
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D008274:Magnesium