A Unifying Mechanism of DNA Translocation Underlying Chromatin Remodeling

Chromatin remodelers are RecA-like DNA translocases that couple to ATP hydrolysis to alter the position and composition of the nucleosome. The mechanism by which chromatin remodelers translocate DNA around nucleosomes has been the subject of debate, and several models have been proposed, including DNA twist, loop, and wave-ratchet-wave models. Recent structures of chromatin-remodeling enzymes, including Snf2, Chd1, ISWI, and Ino80, in complex with nucleosomes have shed light on a conserved mechanism of DNA translocation. By contrast, Swr1 binds at the canonical site on a nucleosome, but induces abnormal DNA distortion and does not possess DNA translocation activity. Chromatin remodelers alter the position and composition of nucleosomes, and play key roles in the regulation of chromatin structure and various chromatin-based transactions. Recent cryo-electron microscopy (cryo-EM) and single-molecule fluorescence resonance energy transfer (smFRET) studies have shed mechanistic light on the fundamental question of how the remodeling enzymes couple with ATP hydrolysis to slide nucleosomes. Structures of the chromatin remodeler Snf2 bound to the nucleosome reveal the conformational cycle of the enzyme and the induced DNA distortion. Investigations on ISWI, Chd1, and INO80 support a unifying fundamental mechanism of DNA translocation. Finally, studies of the SWR1 complex suggest that the enzyme distorts the DNA abnormally to achieve histone exchange without net DNA translocation. Chromatin remodelers alter the position and composition of nucleosomes, and play key roles in the regulation of chromatin structure and various chromatin-based transactions. Recent cryo-electron microscopy (cryo-EM) and single-molecule fluorescence resonance energy transfer (smFRET) studies have shed mechanistic light on the fundamental question of how the remodeling enzymes couple with ATP hydrolysis to slide nucleosomes. Structures of the chromatin remodeler Snf2 bound to the nucleosome reveal the conformational cycle of the enzyme and the induced DNA distortion. Investigations on ISWI, Chd1, and INO80 support a unifying fundamental mechanism of DNA translocation. Finally, studies of the SWR1 complex suggest that the enzyme distorts the DNA abnormally to achieve histone exchange without net DNA translocation. the most common form of DNA in solution. A prominent feature of B-DNA is the presence of two district grooves, a major and a minor groove. the best-known member of the CHD subfamily of chromatin remodelers that is characterized by N-terminal double chromodomains (dCD) and a C-terminal DNA-binding domain (DBD). Chd1 slides nucleosomes to generate evenly spaced nucleosome arrays. ATP-dependent superfamily 2 (SF2) DNA helicase/translocases that regulate accessibility of chromatin DNA. They include diverse enzymes, with four major subfamilies: SWI/SNF, ISWI, CHD, and INO80. a popular biophysical technique based on transmission electron microscopy that is used to determine the structure of a sample at cryogenic temperature. the protein scaffold of nucleosomes that contains two copies of histones H2A, H2B, H3, and H4. Each histone has a tail and a structured core. a large megadalton complex that contains a motor subunit (Ino80), nucleosome-binding subunits (Arp5, Ies6, and Ies2), central scaffold proteins (Rvb1/2, also known as RuvBL1/2), and others. Ino80 has a large subfamily-specific insertion loop in the second RecA-like lobe (lobe 2) that interacts with the Rvb1/2 heterohexamer. the catalytic motor of ISWI subfamily remodeling complexes which slide nucleosomes, generally generate evenly spaced nucleosome arrays, and are involved in chromosomal folding. a biophysical technique to observe local magnetic fields around atomic nuclei. A sample is usually placed in a magnetic field at room temperature, and NMR signals are used to determine the structure of the molecule. the deposition of nucleosomes along genomic DNA is not random. At some genomic regions, such as promoter regions downstream of transcription start-sites and regions flanking the binding sites of the chromatin regulator CTCF, nucleosomes are arranged with a regular spacing. a biophysical technique used to measure distances, wherein a pair of donor and acceptor fluorophores are excited and detected at a single-molecule level. the catalytic subunit of the SWI/SNF complex, which mediates nucleosome sliding and ejection. Snf2 contains a HSA domain and a bromodomain (BD). an effective way to define the rotational orientations of nucleosomal DNA. The major groove of the central base pair (dyad position) is defined as SHL 0. Major grooves along the DNA wrapping path that faces the histone core are denoted SHL ± 1, SHL ± 2, etc. (positive in one direction, negative in the other), whereas the minor grooves that face histones are denoted SHL ± 0.5, SHL ± 1.5, etc. this complex is highly related to the INO80 complex. It contains multiple subunits, including the motor subunit Swr1, DNA-binding subunits Arp6 and Swc6, scaffold proteins RuvBL1/2, H2A.Z recognition protein Swc2, and others. Swr1 has a similar domain structure to Ino80. the motor domain of DNA/RNA translocases typically binds to and travels along one strand of the DNA duplex, which is referred as to the tracking strand, whereas the complementary strand is named the guide strand.