Biggar S R, Crabtree G R
Departments of Developmental Biology and Pathology, Stanford University Medical School, Stanford, CA 94305, USA.
EMBO J. 1999 Apr 15;18(8):2254-64. doi: 10.1093/emboj/18.8.2254.
Chromatin presents a significant obstacle to transcription, but two means of overcoming its repressive effects, histone acetylation and the activities of the Swi-Snf complex, have been proposed. Histone acetylation and Swi-Snf activity have been shown to be crucial for transcriptional induction and to facilitate binding of transcription factors to DNA. By regulating the activity of the Swi-Snf complex in vivo, we found that active transcription requires continuous Swi-Snf function, demonstrating a role for this complex beyond the induction of transcription. Despite the presumably generalized packaging of genes into chromatin, previous studies have indicated that the transcriptional requirements for the histone acetyltransferase, Gcn5, and the Swi-Snf complex are limited to a handful of genes. However, inactivating Swi-Snf function in cells also lacking GCN5 revealed defects in transcription of several genes previously thought to be SWI-SNF- and GCN5-independent. These findings suggest that chromatin remodeling plays a widespread role in gene expression and that these two chromatin remodeling activities perform independent and overlapping functions during transcriptional activation.
染色质对转录构成了重大障碍,但已提出两种克服其抑制作用的方式,即组蛋白乙酰化和Swi-Snf复合物的活性。组蛋白乙酰化和Swi-Snf活性已被证明对转录诱导至关重要,并有助于转录因子与DNA结合。通过在体内调节Swi-Snf复合物的活性,我们发现活跃转录需要Swi-Snf持续发挥功能,这表明该复合物在转录诱导之外还具有作用。尽管基因可能普遍被包装成染色质,但先前的研究表明,组蛋白乙酰转移酶Gcn5和Swi-Snf复合物的转录需求仅限于少数基因。然而,在同样缺乏GCN5的细胞中使Swi-Snf功能失活,揭示了几个先前认为不依赖SWI-SNF和GCN5的基因在转录方面存在缺陷。这些发现表明染色质重塑在基因表达中发挥着广泛作用,并且这两种染色质重塑活性在转录激活过程中执行独立且重叠的功能。