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Regulation of the nucleosome repeat length in vivo by the DNA sequence, protein concentrations and long-range interactions

  • The nucleosome repeat length (NRL) is an integral chromatin property important for its biological functions. Recent experiments revealed several conflicting trends of the NRL dependence on the concentrations of histones and other architectural chromatin proteins, both in vitro and in vivo, but a systematic theoretical description of NRL as a function of DNA sequence and epigenetic determinants is currently lacking. To address this problem, we have performed an integrative biophysical and bioinformatics analysis in species ranging from yeast to frog to mouse where NRL was studied as a function of various parameters. We show that in simple eukaryotes such as yeast, a lower limit for the NRL value exists, determined by internucleosome interactions and remodeler action. For higher eukaryotes, also the upper limit exists since NRL is an increasing but saturating function of the linker histone concentration. Counterintuitively, smaller H1 variants or non-histone architectural proteins can initiate larger effects on the NRL due to entropicThe nucleosome repeat length (NRL) is an integral chromatin property important for its biological functions. Recent experiments revealed several conflicting trends of the NRL dependence on the concentrations of histones and other architectural chromatin proteins, both in vitro and in vivo, but a systematic theoretical description of NRL as a function of DNA sequence and epigenetic determinants is currently lacking. To address this problem, we have performed an integrative biophysical and bioinformatics analysis in species ranging from yeast to frog to mouse where NRL was studied as a function of various parameters. We show that in simple eukaryotes such as yeast, a lower limit for the NRL value exists, determined by internucleosome interactions and remodeler action. For higher eukaryotes, also the upper limit exists since NRL is an increasing but saturating function of the linker histone concentration. Counterintuitively, smaller H1 variants or non-histone architectural proteins can initiate larger effects on the NRL due to entropic reasons. Furthermore, we demonstrate that different regimes of the NRL dependence on histone concentrations exist depending on whether DNA sequence-specific effects dominate over boundary effects or vice versa. We consider several classes of genomic regions with apparently different regimes of the NRL variation. As one extreme, our analysis reveals that the period of oscillations of the nucleosome density around bound RNA polymerase coincides with the period of oscillations of positioning sites of the corresponding DNA sequence. At another extreme, we show that although mouse major satellite repeats intrinsically encode well-defined nucleosome preferences, they have no unique nucleosome arrangement and can undergo a switch between two distinct types of nucleosome positioning.zeige mehrzeige weniger

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Metadaten
Verfasserangaben:Daria A. Beshnova, Andrey G. CherstvyORCiD, Yevhen Vainshtein, Vladimir B. Teif
DOI:https://doi.org/10.1371/journal.pcbi.1003698
ISSN:1553-734X
ISSN:1553-7358
Pubmed ID:https://pubmed.ncbi.nlm.nih.gov/24992723
Titel des übergeordneten Werks (Englisch):PLoS Computational Biology : a new community journal
Verlag:PLoS
Verlagsort:San Fransisco
Publikationstyp:Wissenschaftlicher Artikel
Sprache:Englisch
Jahr der Erstveröffentlichung:2014
Erscheinungsjahr:2014
Datum der Freischaltung:27.03.2017
Band:10
Ausgabe:7
Seitenanzahl:14
Fördernde Institution:Heidelberg Center for Modeling and Simulation in the Biosciences; DKFZ Intramural Grant
Organisationseinheiten:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Physik und Astronomie
Peer Review:Referiert
Publikationsweg:Open Access
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