Disease relevance of ISWI

• Inhibition of ISWI function results in aberrant eye development and the formation of cataracts [1].
• We find that the ability to distort DNA is shared by the yeast SWI/SNF complex, Xenopus Mi-2 complex, recombinant ISWI, and recombinant BRG1, suggesting that the generation of superhelical torsion represents a primary biomechanical activity shared by all Snf2p-related ATPase motors [2].

High impact information on ISWI

• Recreating this exchange in vitro, we identified the chromatin-remodeling nucleosomal adenosine triphosphatase (ATPase) ISWI as a key molecule in this process [3].
• ISWI actively erases the TATA binding protein from association with the nuclear matrix [3].
• We found the conserved N termini (the N-terminal tails) of histone H4 essential to stimulate ISWI ATPase activity, in contrast to other histone tails [4].
• The ATPase ISWI can be considered the catalytic core of several multiprotein nucleosome remodeling machines [4].
• Despite the poor spacing of nucleosomes, ISWI depletion has little effect on DNA replication, chromosome condensation or sister chromatid cohesion in the cell-free extracts [5].

Biological context of ISWI

• These data suggest a critical role for ISWI chromatin remodeling complexes in neural development, including eye differentiation, in the Xenopus laevis embryo [1].
• Expression of ISWI and its binding to chromatin during the cell cycle and early development [6].

Anatomical context of ISWI

• Four distinct ISWI complexes have been identified in Xenopus oocytes [1].
• Whole mount in situ hybridization shows ISWI localized in the lateral sides of the neural plate, brain, eye, and in later stages, the spinal cord [1].
• Injection of antisense ISWI RNA, morpholino oligonucleotides or dominant-negative ISWI mutant mRNA into fertilized eggs inhibits gastrulation and neural fold closure [1].

Other interactions of ISWI

• Critical role for the histone H4 N terminus in nucleosome remodeling by ISWI [4].
• Nucleosome assembly also occurs in ISWI-depleted extracts, but nucleosome spacing is disturbed [6].

References