Altered binding of human histone gene transcription factors during the shutdown of proliferation and onset of differentiation in HL-60 cells.
Altered binding of human histone gene transcription factors during the shutdown of proliferation and onset of differentiation in HL-60 cells.
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在 HL-60 细胞增殖停止和分化开始期间改变人组蛋白基因转录因子的结合。
DOI：
10.1073/pnas.86.6.1865
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发表时间：
1989
影响因子：
11.1
通讯作者：
vanWijnen,A
中科院分区：
文献类型：
--
作者：
Stein,G;Lian,J;Stein,J;Briggs,R;Shalhoub,V;Wright,K;Pauli,U;vanWijnen,A
两个网站的蛋白质-DNA相互作用已被确定在体内和体外的近端启动子区的H4和H3人类组蛋白基因。在增殖细胞中，这些基因在整个细胞周期中转录，并且更远的位点I和近端位点II都被启动子结合因子占据。在这份报告中，我们证明，在关闭的增殖和人类早幼粒细胞白血病细胞系HL-60分化成细胞表现出单核细胞的表型特性，组蛋白基因表达下调的转录水平。在分化的HL-60细胞中，启动子因子在体内占据位点I，但位点II的蛋白质-DNA相互作用选择性丧失。此外，在体外结合活性的位点II启动子因子HiNF-D是在分化的细胞中丢失，和核提取物从分化的细胞不支持这些组蛋白基因的体外转录。我们的研究结果表明，HiNF-D与近端启动子位点II序列的相互作用在使细胞生长调节组蛋白基因在增殖细胞中转录中起主要作用。似乎虽然组蛋白基因表达的细胞周期控制由转录和mRNA稳定性介导，但随着增殖的停止和mRNA稳定性的开始，随着增殖的停止和分化的开始，组蛋白基因表达在转录水平上受到调节。
Two sites of protein-DNA interaction have been identified in vivo and in vitro in the proximal promoter regions of an H4 and an H3 human histone gene. In proliferating cells, these genes are transcribed throughout the cell cycle, and both the more distal site I and the proximal site II are occupied by promoter-binding factors. In this report we demonstrate that during the shutdown of proliferation and onset of differentiation of the human promyelocytic leukemia cell line HL-60 into cells that exhibit phenotypic properties of monocytes, histone gene expression is down-regulated at the level of transcription. In vivo occupancy of site I by promoter factors persists in the differentiated HL-60 cells, but protein-DNA interactions at site II are selectively lost. Furthermore, in vitro binding activity of the site II promoter factor HiNF-D is lost in differentiated cells, and nuclear extracts from differentiated cells do not support in vitro transcription of these histone genes. Our results suggest that the interaction of HiNF-D with proximal promoter site II sequences plays a primary role in rendering cell growth-regulated histone genes transcribable in proliferating cells. It appears that while cell-cycle control of histone gene expression is mediated by both transcription and mRNA stability, with the shutdown of proliferation and onset mRNA stability, with the shutdown of proliferation and onset of differentiation, histone gene expression is regulated at the transcriptional level.