HISTONE H2AX GENE-TRANSCRIPTION IS REGULATED DIFFERENTLY THAN TRANSCRIPTION OF OTHER REPLICATION-LINKED HISTONE GENES
HISTONE H2AX GENE-TRANSCRIPTION IS REGULATED DIFFERENTLY THAN TRANSCRIPTION OF OTHER REPLICATION-LINKED HISTONE GENES
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DOI：
10.1128/mcb.13.2.984
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发表时间：
1993-02-01
影响因子：
5.3
通讯作者：
HATCH, CL
中科院分区：
文献类型：
--
作者：
BONNER, WM;MANNIRONI, C;HATCH, CL
组蛋白H2A。X是一种与复制无关的组蛋白H2A同工蛋白，其编码由转录本在3'端交替加工，产生两个mRNA：一个0.6 kb的mRNA以复制相关组蛋白的茎环结构特征结束，另一个1.6 kb的mRNA以约1kb的下游结尾（C. Mannironi， W. M. Bonner, and C. L. Hatch, Nucleic Acids Res. 17: 913 -9126, 1989）。其中，0.6 kb的H2A。X茎环mRNA在许多细胞系中占主导地位，这表明两种mRNA的存在可能不能完全解释H2A的复制独立性。X蛋白合成。通过发现0.6 kb H2A的水平，解决了这种模糊性。X mRNA在抑制DNA复制时仅弱下调，在抑制蛋白质合成时仅弱上调，而其他复制相关mRNA的水平在这两种条件下均强烈下调或上调。对特定H2A基因的核转录率分析表明，在抑制DNA合成过程中，复制链型H2A基因的转录率大幅下降，而在抑制蛋白质合成过程中，复制链型H2A基因的转录率大幅上升。X基因转录在两种条件下均略有下降。这些差异在H2A之间的转录调控。X基因和其他复制相关组蛋白基因足以解释其各自茎环mrna调控的差异。
Histone H2A.X is a replication-independent histone H2A isoprotein species that is encoded by a transcript alternatively processed at the 3' end to yield two mRNAs: a 0.6-kb mRNA ending with the stem-loop structure characteristic of the mRNAs for replication-linked histone species, and a second, polyadenylated 1.6-kb mRNA ending about 1 kb further downstream (C. Mannironi, W. M. Bonner, and C. L. Hatch, Nucleic Acids Res. 17:9113-9126, 1989). Of the two, the 0.6-kb H2A.X stem-loop mRNA predominates in many cell lines, indicating that the presence of two types of mRNA may not completely account for the replication independence of H2A.X protein synthesis. The ambiguity is resolved by the finding that the level of the 0.6-kb H2A.X mRNA is only weakly downregulated during the inhibition of DNA replication and only weakly upregulated during the inhibition of protein synthesis, while the levels of other replication-linked mRNAs are strongly down- or upregulated under these two conditions. Analysis of the nuclear transcription rates of specific H2A genes showed that while the rates of transcription of replication-linked H2A genes decreased substantially during the inhibition of DNA synthesis and increased substantially during the inhibition of protein synthesis, the rate of H2A.X gene transcription decreased slightly under both conditions. These differences in transcriptional regulation between the H2A.X gene and other replication-linked histone genes are sufficient to account for the differences in regulation of their respective stem-loop mRNAs.