Khochbin S, Wolffe A P
Laboratory of Molecular Embryology, National Institutes of Child Health and Human Development, NIH, Bethesda, MD 20892.
Gene. 1993 Jun 30;128(2):173-80. doi: 10.1016/0378-1119(93)90560-p.
We have isolated genomic clones of the Xenopus laevis histone H1(0) promoter and identified regulatory elements mediating the transcriptional regulation of the H1(0) gene. Expression of H1(0) is associated with the terminal differentiation of many cell types. During X. laevis development, H1(0) mRNA is present in the oocyte and egg, but remains at low levels during embryogenesis until hatching. After this time, mRNA levels accumulate dramatically correlating with the differentiation of many tissue types, e.g., liver and skin. Accumulation of H1(0) mRNA can be induced at earlier development stages by treating embryos with butyrate. The enhanced transcription of H1(0) in adult somatic cells, as well as the butyrate inducibility of the gene, have been investigated using transfection of adult X. laevis A6 somatic cells. We have defined specific protein-nucleic acid interactions with three cis-acting elements. Two previously defined gene regulatory elements: the H1 box, normally involved in the regulation of the H1 gene, and the H4TF2 site, normally involved in the regulation of the H4 gene, appear to have novel roles in determining differentiation-specific H1(0) expression. These two elements act together with a new distal cis-acting element in order to sustain high levels of basal transcription and to potentiate transcription following butyrate treatment.
我们分离出了非洲爪蟾组蛋白H1(0)启动子的基因组克隆,并鉴定了介导H1(0)基因转录调控的调控元件。H1(0)的表达与许多细胞类型的终末分化相关。在非洲爪蟾发育过程中,H1(0) mRNA存在于卵母细胞和卵子中,但在胚胎发生期间一直保持低水平,直到孵化。在此之后,mRNA水平急剧积累,与许多组织类型(如肝脏和皮肤)的分化相关。通过用丁酸盐处理胚胎,可以在早期发育阶段诱导H1(0) mRNA的积累。利用成年非洲爪蟾A6体细胞转染技术,研究了成年体细胞中H1(0)的增强转录以及该基因的丁酸盐诱导性。我们已经确定了与三个顺式作用元件的特定蛋白质-核酸相互作用。两个先前定义的基因调控元件:通常参与H1基因调控的H1盒和通常参与H4基因调控的H4TF2位点,似乎在决定分化特异性H1(0)表达中具有新的作用。这两个元件与一个新的远端顺式作用元件共同作用,以维持高水平的基础转录,并在丁酸盐处理后增强转录。