Sera T, Wolffe A P
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892-5431, USA.
Mol Cell Biol. 1998 Jul;18(7):3668-80. doi: 10.1128/MCB.18.7.3668.
We explore the role of histone H1 as a DNA sequence-dependent architectural determinant of chromatin structure and of transcriptional activity in chromatin. The Xenopus laevis oocyte- and somatic-type 5S rRNA genes are differentially transcribed in embryonic chromosomes in vivo depending on the incorporation of somatic histone H1 into chromatin. We establish that this effect can be reconstructed at the level of a single nucleosome. H1 selectively represses oocyte-type 5S rRNA genes by directing the stable positioning of a nucleosome such that transcription factors cannot bind to the gene. This effect does not occur on the somatic-type genes. Histone H1 binds to the 5' end of the nucleosome core on the somatic 5S rRNA gene, leaving key regulatory elements in the promoter accessible, while histone H1 binds to the 3' end of the nucleosome core on the oocyte 5S rRNA genes, specifically blocking access to a key promoter element (the C box). TFIIIA can bind to the somatic 5S rRNA gene assembled into a nucleosome in the presence of H1. Because H1 binds with equivalent affinities to nucleosomes containing either gene, we establish that it is the sequence-selective assembly of a specific repressive chromatin structure on the oocyte 5S rRNA genes that accounts for differential transcriptional repression. Thus, general components of chromatin can determine the assembly of specific regulatory nucleoprotein complexes.
我们探讨了组蛋白H1作为染色质结构及染色质转录活性的DNA序列依赖性结构决定因素的作用。非洲爪蟾卵母细胞型和体细胞型5S rRNA基因在体内胚胎染色体中的转录存在差异,这取决于体细胞组蛋白H1掺入染色质的情况。我们证实,这种效应可以在单个核小体水平上重现。H1通过引导核小体的稳定定位来选择性抑制卵母细胞型5S rRNA基因,从而使转录因子无法结合到该基因上。这种效应在体细胞型基因上不会发生。组蛋白H1与体细胞5S rRNA基因核小体核心的5'端结合,使启动子中的关键调控元件保持可及状态,而组蛋白H1与卵母细胞5S rRNA基因核小体核心的3'端结合,特异性地阻断对一个关键启动子元件(C盒)的访问。在H1存在的情况下,TFIIIA可以结合到组装成核小体的体细胞5S rRNA基因上。由于H1与含有这两种基因的核小体具有同等亲和力,我们证实,正是卵母细胞5S rRNA基因上特定抑制性染色质结构的序列选择性组装导致了差异转录抑制。因此,染色质的一般成分可以决定特定调节性核蛋白复合物的组装。