Nucleosome spacing generated by ISWI and CHD1 remodelers is constant regardless of nucleosome density.
Arrays of regularly spaced nucleosomes are a hallmark of chromatin, but it remains unclear how they are generated. Recent genome-wide studies, in vitro and in vivo, showed constant nucleosome spacing even if the histone concentration was experimentally reduced. This counters the long-held assumption that nucleosome density determines spacing and calls for factors keeping spacing constant regardless of nucleosome density. We call this a clamping activity. Here, we show in a purified system that ISWI- and CHD1-type nucleosome remodelers have a clamping activity such that they not only generate regularly spaced nucleosome arrays but also generate constant spacing regardless of nucleosome density. This points to a functionally attractive nucleosome interaction that could be mediated either directly by nucleosome-nucleosome contacts or indirectly through the remodelers. Mutant Drosophila melanogaster ISWI without the Hand-Sant-Slide (HSS) domain had no detectable spacing activity even though it is known to remodel and slide nucleosomes. This suggests that the role of ISWI remodelers in generating constant spacing is not just to mediate nucleosome sliding; they actively contribute to the attractive interaction. Additional factors are necessary to set physiological spacing in absolute terms.
Adolf Butenandt Institute, Molecular Biology, University of Munich, Munich, Germany.
Corinna
C
Lieleg
Walter Schottky Institute, Physics Department, Technical University of Munich, Garching near Munich, Germany.
Philip
P
Ketterer
Theory of Complex Biosystems, Physics Department, Technical University of Munich, Garching near Munich, Germany.
Johannes
J
Nuebler
Adolf Butenandt Institute, Molecular Biology, University of Munich, Munich, Germany.
Johanna
J
Ludwigsen
Theory of Complex Biosystems, Physics Department, Technical University of Munich, Garching near Munich, Germany.
Ulrich
U
Gerland
Walter Schottky Institute, Physics Department, Technical University of Munich, Garching near Munich, Germany.
Hendrik
H
Dietz
Adolf Butenandt Institute, Molecular Biology, University of Munich, Munich, Germany felix.mueller-planitz@med.uni-muenchen.de pkorber@lmu.de.
Felix
F
Mueller-Planitz
Adolf Butenandt Institute, Molecular Biology, University of Munich, Munich, Germany felix.mueller-planitz@med.uni-muenchen.de pkorber@lmu.de.
Philipp
P
Korber
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000737:chemistry / Q000378:metabolism*; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
C489847:CHD1 protein, S cerevisiae; D004268:DNA-Binding Proteins; C086468:ISWI protein; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000251:Adenosine Triphosphatases