Dong Y, Liu D, Skoultchi A I
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461.
Mol Cell Biol. 1995 Apr;15(4):1889-900. doi: 10.1128/MCB.15.4.1889.
The replacement linker histone H1 (zero) is associated with terminal differentiation in many mammalian cell types, and its accumulation in chromatin may contribute to transcriptional repression occurring during terminal differentiation. H1 (zero) also accumulates in a variety of cell culture lines undergoing terminal differentiation. During in vitro mouse erythroleukemia cell differentiation, H1 (zero) gene expression is induced very rapidly, prior to the time when the cells actually commit to terminal differentiation. We have used a combination of transfection assays and in vitro DNA-protein interaction studies to identify nuclear protein binding sites in the H1 (zero) promoter that control expression and induction of the H1(zero) gene in mouse erythroleukemia cells. The results indicate that transcription of the H1 (zero) gene is controlled by three elements present in the upstream region of the promoter between positions -305 and -470. Site-directed mutagenesis of each of these elements showed that one of them controls inducibility of the gene in differentiating cells. The other two elements in the upstream control region affect primarily the level of transcription of the gene in undifferentiated and differentiating cells. These two elements share a DNA sequence motif consisting of a (dG)6 tract contained in an eight-base consensus, (A/C)GGGGGG(A/C). Additional copies of this motif are present elsewhere in the H1 (zero) promoter.
替代连接组蛋白H1（零）与许多哺乳动物细胞类型的终末分化相关，其在染色质中的积累可能有助于终末分化过程中发生的转录抑制。H1（零）也在经历终末分化的多种细胞系中积累。在体外小鼠红白血病细胞分化过程中，H1（零）基因表达在细胞实际进入终末分化之前就迅速被诱导。我们使用转染分析和体外DNA-蛋白质相互作用研究相结合的方法，来鉴定H1（零）启动子中控制小鼠红白血病细胞中H1（零）基因表达和诱导的核蛋白结合位点。结果表明，H1（零）基因的转录受启动子上游-305至-470位置之间存在的三个元件控制。对这些元件中的每一个进行定点诱变表明，其中一个元件控制分化细胞中该基因的诱导性。上游控制区中的另外两个元件主要影响未分化和分化细胞中该基因的转录水平。这两个元件共享一个由八碱基共有序列（A/C）GGGGGG（A/C）中的（dG）6序列组成的DNA序列基序。该基序的额外拷贝存在于H1（零）启动子的其他位置。
