DNA methylation and chromatin structure regulate PU.1 expression
DNA methylation and chromatin structure regulate PU.1 expression
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DOI：
10.1089/104454999314737
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发表时间：
1999-12-01
影响因子：
3.1
通讯作者：
Klemsz, MJ
中科院分区：
文献类型：
--
作者：
Amaravadi, L;Klemsz, MJ
基因敲除研究表明，PU.1是许多血细胞谱系正常发育所必需的，但这种转录因子在红系细胞中的过表达可导致红白血病。因此，PU.1的组织特异性表达是如何调节的，对于我们理解造血是很重要的。在这项研究中，我们发现，B和巨噬细胞系表达PU.1包含DNA酶I-高敏感位点的内含子1和低甲基化在3个MspI位点侧翼外显子1。使用几种T细胞系的研究结果表明，随着这些细胞的成熟，甲基化模式发生了变化。一个前T细胞系，表达PU.1包含DNA酶I-超敏位点的内含子1，也是低甲基化的两个MspI网站。其他未成熟T细胞系至少有一个MspI位点甲基化，没有显示超敏位点。成熟T细胞系的甲基化模式更类似于成纤维细胞的甲基化模式。用5-氮杂胞苷处理未成熟T细胞系导致PU，1转录物的表达。这些数据表明，PU.1的组织特异性表达受染色质结构和DNA甲基化控制，这可能是造血过程中用于关闭特定细胞系中PU.1表达的机制。
Knockout studies have shown that PU.1 is required for the normal development of many blood cell lineages, yet overexpression of this transcription factor in erythroid cells can lead to erythroleukemia. Thus, how the tissue-specific expression of PU.1 is regulated is important to our understanding of hematopoiesis. In this study, we showed that B and macrophage cell lines expressing PU.1 contained DNase I-hypersensitive sites in intron 1 and were hypomethylated at three MspI sites flanking exon 1. Results from studies using several T-cell lines suggested that the pattern of methylation changed as these cells matured. A pre-T cell line that expresses PU.1 contained DNase I-hypersensitive sites in intron 1 and was also hypomethylated at both MspI sites. Other immature T-cell lines had methylated at least one of the MspI sites and displayed no hypersensitive sites, Mature T-cell lines had a methylation pattern more similar to that of fibroblasts, Treatment of an immature T-cell line with 5-azacytidine resulted in the expression of PU,1 transcripts. These data suggest that the tissue-specific expression of PU.1 is controlled by chromatin structure and DNA methylation and that this may be a mechanism used to shut off PU.1 expression in specific cell lineages during hematopoiesis.