TY - JOUR
T1 - XNucleosome-free region dominates histone acetylation in targeting SWR1 to promoters for H2A.Z replacement
AU - Ranjan, Anand
AU - Mizuguchi, Gaku
AU - Fitzgerald, Peter C.
AU - Wei, Debbie
AU - Wang, Feng
AU - Huang, Yingzi
AU - Luk, Ed
AU - Woodcock, Christopher L.
AU - Wu, Carl
N1 - Funding Information:
We thank Dr. Joseph Wall, STEM facility, Biology Department, Brookhaven Laboratories, Upton, NY, and his staff for conducting STEM mass measurements; Karolin Luger’s laboratory for sharing unpublished data on Swc2; Wei-Hua Wu for the kind gift of yeast strains; Sameet Mehta for bioinformatics; and Michael Lichten, Sean Eddy, Claude Klee, Joseph Landry, members of our laboratory and reviewers for helpful comments. This work was supported by a Leukemia and Lymphoma Society fellowship (to A.R.), by the Janelia Farm Research Campus, Howard Hughes Medical Institute (to C.W. and G.M.), and by the Center for Cancer Research, National Cancer Institute.
PY - 2013/9/12
Y1 - 2013/9/12
N2 - The histone variant H2A.Z is a genome-wide signature of nucleosomes proximal to eukaryotic regulatory DNA. Whereas the multisubunit chromatin remodeler SWR1 is known to catalyze ATP-dependent deposition of H2A.Z, the mechanism of SWR1 recruitment to S. cerevisiae promoters has been unclear. A sensitive assay for competitive binding of dinucleosome substrates revealed that SWR1 preferentially binds long nucleosome-free DNA and the adjoining nucleosome core particle, allowing discrimination of gene promoters over gene bodies. Analysis of mutants indicates that the conserved Swc2/YL1 subunit and the adenosine triphosphatase domain of Swr1 are mainly responsible for binding to substrate. SWR1 binding is enhanced on nucleosomes acetylated by the NuA4 histone acetyltransferase, but recognition of nucleosome-free and nucleosomal DNA is dominant over interaction with acetylated histones. Such hierarchical cooperation between DNA and histone signals expands the dynamic range of genetic switches, unifying classical gene regulation by DNA-binding factors with ATP-dependent nucleosome remodeling and posttranslational histone modifications.
AB - The histone variant H2A.Z is a genome-wide signature of nucleosomes proximal to eukaryotic regulatory DNA. Whereas the multisubunit chromatin remodeler SWR1 is known to catalyze ATP-dependent deposition of H2A.Z, the mechanism of SWR1 recruitment to S. cerevisiae promoters has been unclear. A sensitive assay for competitive binding of dinucleosome substrates revealed that SWR1 preferentially binds long nucleosome-free DNA and the adjoining nucleosome core particle, allowing discrimination of gene promoters over gene bodies. Analysis of mutants indicates that the conserved Swc2/YL1 subunit and the adenosine triphosphatase domain of Swr1 are mainly responsible for binding to substrate. SWR1 binding is enhanced on nucleosomes acetylated by the NuA4 histone acetyltransferase, but recognition of nucleosome-free and nucleosomal DNA is dominant over interaction with acetylated histones. Such hierarchical cooperation between DNA and histone signals expands the dynamic range of genetic switches, unifying classical gene regulation by DNA-binding factors with ATP-dependent nucleosome remodeling and posttranslational histone modifications.
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U2 - 10.1016/j.cell.2013.08.005
DO - 10.1016/j.cell.2013.08.005
M3 - Article
C2 - 24034247
AN - SCOPUS:84884214357
SN - 0092-8674
VL - 154
SP - 1232
JO - Cell
JF - Cell
IS - 6
ER -