Abstract
ATP-dependent chromatin remodellers modulate nucleosome dynamics by mobilizing or disassembling nucleosomes, as well as altering nucleosome composition. These chromatin remodellers generally function by translocating along nucleosomal DNA at the H3–H4 interface of nucleosomes. Here we show that, unlike other remodellers, INO80 translocates along DNA at the H2A–H2B interface of nucleosomes and persistently displaces DNA from the surface of H2A–H2B. DNA translocation and DNA torsional strain created near the entry site of nucleosomes by INO80 promotes both the mobilization of nucleosomes and the selective exchange of H2A.Z–H2B dimers out of nucleosomes and replacement by H2A–H2B dimers without any additional histone chaperones. We find that INO80 translocates and mobilizes H2A.Z-containing nucleosomes more efficiently than those containing H2A, partially accounting for the preference of INO80 to replace H2A.Z with H2A. Our data suggest that INO80 has a mechanism for dimer exchange that is distinct from other chromatin remodellers including its paralogue SWR1.
Highlights
adenosine triphosphate (ATP)-dependent chromatin remodellers modulate nucleosome dynamics by mobilizing or disassembling nucleosomes, as well as altering nucleosome composition
Here we investigate the interactions of Saccharomyces cerevisiae INO80 ATPase domain with nucleosome, the effects of deoxyribonucleic acid (DNA) translocation by INO80 on histone–DNA interactions, the role of translocation in altering nucleosome dynamics and its potential in leading to nucleosome movement and dimer exchange
We find that INO80 translocates on nucleosomal DNA at the H2A–H2B dimer interface causing DNA to be persistently displaced from the dimer surface
Summary
ATP-dependent chromatin remodellers modulate nucleosome dynamics by mobilizing or disassembling nucleosomes, as well as altering nucleosome composition. INO80 potentially exchanges histone dimers, and mobilizes and spaces nucleosomes[36] Other factors, such as the transcription complex, may have a role as important or more than INO80 in facilitating the exchange of H2A.Z at active promoters[37]. The mechanisms of nucleosome spacing, nucleosome assembly and disassembly by ATP-dependent nucleosome remodellers have been extensively studied[38,39], relatively little is known about the role of ATP hydrolysis and DNA translocation in the SWR1/INO80 family of remodellers for exchanging histone dimers. Remodelling complexes of the ISWI and SWI/SNF families are known to engage and translocate along DNA deep inside of nucleosomes near the dyad axis at superhelical location (SHL) À 2 (refs 39–42) These remodellers are efficient in repositioning nucleosomes for either nucleosome spacing or disassembly[43]. It is not evident yet how translocation of the ATPase domain on nucleosomal DNA leads or contributes to histone dimer exchange
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