Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Repressive chromatin structures need to be unravelled to allow DNA-binding proteins access to their target sequences. This de-repression constitutes an important point at which transcription and presumably other nuclear processes can be regulated. Energy-consuming enzyme complexes that facilitate the interaction of transcription factors with chromatin by modifying nucleosome structure are involved in this regulation. One such factor, nucleosome-remodelling factor (NURF), has been isolated from Drosophila embryo extracts. We have now identified a chromatin-accessibility complex (CHRAC) which uses energy to increase the general accessibility of DNA in chromatin. However, unlike other known chromatin remodelling factors, CHRAC can also function during chromatin assembly: it uses ATP to convert irregular chromatin into a regular array of nucleosomes with even spacing. CHRAC combines enzymes that modulate nucleosome structure and DNA topology. Using mass spectrometry, we identified two of the five CHRAC subunits as the ATPase ISWI, which is also part of NURF, and topoisomerase II. The presence of ISWI in different contexts suggests that chromatin remodelling machines have a modular nature and that ISWI has a central role in different chromatin remodelling reactions.
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PMID:Chromatin-remodelling factor CHRAC contains the ATPases ISWI and topoisomerase II. 925 92

Chromatin remodelling complexes containing the nucleosome-dependent ATPase ISWI were first isolated from Drosophila embryos (NURF, CHRAC and ACF). ISWI was the only common component reported in these complexes. Our purification of human CHRAC (HuCHRAC) shows that ISWI chromatin remodelling complexes can have a conserved subunit composition in completely different cell types, suggesting a conserved function of ISWI. We show that the human homologues of two novel putative histone-fold proteins in Drosophila CHRAC are present in HuCHRAC. The two human histone-fold proteins form a stable complex that binds naked DNA but not nucleosomes. HuCHRAC also contains human ACF1 (hACF1), the homologue of Acf1, a subunit of Drosophila ACF. The N-terminus of mouse ACF1 was reported as a heterochromatin-targeting domain. hACF1 is a member of a family of proteins with a related domain structure that all may target heterochromatin. We discuss a possible function for HuCHRAC in heterochromatin dynamics. HuCHRAC does not contain topoisomerase II, which was reported earlier as a subunit of Drosophila CHRAC.
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PMID:HuCHRAC, a human ISWI chromatin remodelling complex contains hACF1 and two novel histone-fold proteins. 1088 Apr 50

The chromatin accessibility complex (CHRAC) was originally defined biochemically as an ATP-dependent 'nucleosome remodelling' activity. Central to its activity is the ATPase ISWI, which catalyses the transfer of histone octamers between DNA segments in cis. In addition to ISWI, four other potential subunits were observed consistently in active CHRAC fractions. We have now identified the p175 subunit of CHRAC as Acf1, a protein known to associate with ISWI in the ACF complex. Interaction of Acf1 with ISWI enhances the efficiency of nucleosome sliding by an order of magnitude. Remarkably, it also modulates the nucleosome remodelling activity of ISWI qualitatively by altering the directionality of nucleosome movements and the histone 'tail' requirements of the reaction. The Acf1-ISWI heteromer tightly interacts with the two recently identified small histone fold proteins CHRAC-14 and CHRAC-16. Whether topoisomerase II is an integral subunit has been controversial. Refined analyses now suggest that topoisomerase II should not be considered a stable subunit of CHRAC. Accordingly, CHRAC can be molecularly defined as a complex consisting of ISWI, Acf1, CHRAC-14 and CHRAC-16.
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PMID:Acf1, the largest subunit of CHRAC, regulates ISWI-induced nucleosome remodelling. 1144 19

DNA supercoiling factor (SCF) is a protein capable of generating negative supercoils in DNA in conjunction with topoisomerase II. To clarify the biological functions of SCF, we introduced a heritable SCF RNAi into Drosophila. Upon knockdown of SCF, we observed male lethality and male-specific reduction in the expression levels of X-linked genes. SCF functionally interacts with components of the MSL complex, which are required for dosage compensation via hypertranscription of the male X chromosome. Moreover, SCF colocalizes with the MSL complex along the male X chromosome. Upon overexpression of SCF, the male X chromosome had a bloated appearance. This phenotype was dependent on the histone acetyltransferase MOF and was suppressed by simultaneous overexpression of ISWI. These findings demonstrate that SCF plays a role in transcriptional activation via alteration of chromatin structure and provide evidence that SCF contributes to dosage compensation.
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PMID:DNA supercoiling factor contributes to dosage compensation in Drosophila. 1703 93