Badenhorst Paul, Voas Matthew, Rebay Ilaria, Wu Carl
Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda Maryland 20892-4255, USA.
Genes Dev. 2002 Dec 15;16(24):3186-98. doi: 10.1101/gad.1032202.
The nucleosome remodeling factor (NURF) is one of several ISWI-containing protein complexes that catalyze ATP-dependent nucleosome sliding and facilitate transcription of chromatin in vitro. To establish the physiological requirements of NURF, and to distinguish NURF genetically from other ISWI-containing complexes, we isolated mutations in the gene encoding the large NURF subunit, nurf301. We confirm that NURF is required for transcription activation in vivo. In animals lacking NURF301, heat-shock transcription factor binding to and transcription of the hsp70 and hsp26 genes are impaired. Additionally, we show that NURF is required for homeotic gene expression. Consistent with this, nurf301 mutants recapitulate the phenotypes of Enhancer of bithorax, a positive regulator of the Bithorax-Complex previously localized to the same genetic interval. Finally, mutants in NURF subunits exhibit neoplastic transformation of larval blood cells that causes melanotic tumors to form.
核小体重塑因子(NURF)是几种含ISWI的蛋白复合物之一,它在体外催化ATP依赖的核小体滑动并促进染色质转录。为了确定NURF的生理需求,并在基因层面将NURF与其他含ISWI的复合物区分开来,我们分离出了编码NURF大亚基nurf301的基因突变。我们证实NURF在体内转录激活过程中是必需的。在缺乏NURF301的动物中,热休克转录因子与hsp70和hsp26基因的结合及转录均受到损害。此外,我们表明NURF对于同源异型基因的表达是必需的。与此一致的是,nurf301突变体重现了双胸复合体增强子的表型,双胸复合体增强子是之前定位在相同基因区间的双胸复合体的一个正向调节因子。最后,NURF亚基的突变体表现出幼虫血细胞的肿瘤转化,导致黑色素瘤形成。