Birren B W, Taplitz S J, Herschman H R
Laboratory of Biomedical and Environmental Sciences, University of California, Los Angeles 90024.
Mol Cell Biol. 1987 Nov;7(11):3863-70. doi: 10.1128/mcb.7.11.3863-3870.1987.
We examined in the H4IIE rat hepatoma cell line the relationship between butyrate-induced changes in the nuclease sensitivity of chromatin and changes in transcriptional activity of specific genes. The butyrate-inducible metallothionein I (MT-I) gene underwent a dramatic increase in DNase I sensitivity after 3 h of butyrate treatment. However, genes not transcribed in H4IIE cells underwent the same changes in DNase I sensitivity. Thus, butyrate-induced increases in DNase I sensitivity are not sufficient for the transcriptional activation of a gene. Butyrate treatment has also been reported to alter the sensitivity of sequences to micrococcal nuclease (MNase) in a manner reflecting their tissue-specific expression. Butyrate exposure caused increased digestion of the MT-I gene by MNase. However, butyrate-induced MNase sensitivity also occurred for genes which are neither transcribed in untreated cells nor butyrate inducible. Moreover, cadmium, a potent transcriptional activator of the MT-I gene, does not alter the sensitivity of the MT-I gene to MNase. Thus, the butyrate-induced alterations in MNase sensitivity are neither sufficient for, necessary for, nor indicative of transcriptional activation.
我们在H4IIE大鼠肝癌细胞系中研究了丁酸盐诱导的染色质核酸酶敏感性变化与特定基因转录活性变化之间的关系。丁酸盐诱导的金属硫蛋白I（MT-I）基因在丁酸盐处理3小时后，对DNA酶I的敏感性急剧增加。然而，在H4IIE细胞中不转录的基因对DNA酶I敏感性也发生了相同的变化。因此，丁酸盐诱导的DNA酶I敏感性增加不足以实现基因的转录激活。据报道，丁酸盐处理还以反映其组织特异性表达的方式改变了序列对微球菌核酸酶（MNase）的敏感性。丁酸盐暴露导致MNase对MT-I基因的消化增加。然而，对于在未处理细胞中不转录且对丁酸盐无诱导性的基因，也会出现丁酸盐诱导的MNase敏感性。此外，镉是MT-I基因的强效转录激活剂，但它不会改变MT-I基因对MNase的敏感性。因此，丁酸盐诱导的MNase敏感性变化对于转录激活既不充分，也不必要，也不具有指示性。
