Nucleosome Movement by CHRAC and ISWI without Disruption or trans-Displacement of the Histone Octamer

Abstract

The chromatin accessibility complex (CHRAC) belongs to the class of nucleosome remodeling factors that increase the accessibility of nucleosomal DNA in an ATP-dependent manner. We found that CHRAC induces movements of intact histone octamers to neighboring DNA segments without facilitating their displacement to competing DNA or histone chaperones in trans. CHRAC-induced energy-dependent nucleosome sliding may, in principle, explain nucleosome remodeling, nucleosome positioning, and nucleosome spacing reactions known to be catalyzed by CHRAC. The catalytic core of CHRAC, the ATPase ISWI, also mobilized nucleosomes at the expense of energy. However, the directionality of the CHRAC- and ISWI-induced nucleosome movements differed drastically, indicating that the geometry of the native complex modulates the activity of its catalytic core.

Chromatin remodeling by ATP‐dependent molecular machines

“…(56,(64)(65)(66)(67)(68)(69)(70) These findings indicate that the SNF2-like ATPase polypeptides possess an intrinsic chromatin-remodeling function.…”

“…(71) In the ACF and CHRAC complexes, the Acf1 subunit stimulates the intrinsic chromatin assembly and remodeling activities of ISWI. (30,31,33,67,69) The Acf1 subunit also contains a DNA- binding region that is important for the chromatin assembly activity of ACF. (30) Moreover, Acf1 affects the ability of ISWI to mobilize nucleosomes.…”

“…ISWI alone will catalyze the movement of a nucleosome toward the ends of short (<400 bp) DNA fragments, whereas ACF (¼Acf1 þ ISWI) catalyzes the movement of nucleosomes toward the center of the same DNA fragments. (67,69) Thus, the specialized biochemical properties of the NURF and ACF/CHRAC complexes are determined by their respective NURF301 and Acf1 subunits.…”

“…(1) Nuclease I digestion assays have revealed that SNF2 subfamily complexes disrupt histone-DNA contacts in mononucleosomes, (41,74,75,76) whereas this disruption of histone-DNA contacts was not seen in analogous experiments with ISWI subfamily members. (68,69) (2) Chromatin-remodeling factors can catalyze mobilization (which is sometimes termed 'sliding') of nucleosomes relative to the DNA template. (52,59,63,69,71,(77)(78)(79)(80)(81)(82)(83) (3) SNF2 subfamily complexes, but not ISWI subfamily complexes, can mediate the transfer of histones from one DNA template to a separate DNA template.…”

Mechanisms of ATP dependent chromatin remodeling

“…The SANT domain is similar to the putative DNA binding domains of the ADA HAT complexes, the transcriptional co-repressor N-CoR and the transcription factor TFIIIB [81]. This has prompted speculations that the SANT domain might be responsible for the nonspecific binding of ISWI complexes to DNA and their preferential binding to nucleosomes containing linker DNA over core nucleosomes [82]. The complexes in this group are relatively smaller (300-800 kDa) and contain fewer subunits ranging from 2-4 as compared with the larger complexes in the SNF2, CHD and INO80 subfamilies which contain up to 15 subunits and are often ∼2 mDa.…”