期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1987
卷号：84
期号：8
页码：2135-2139
DOI：10.1073/pnas.84.8.2135
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：We have examined the chromatin structure of the 5'-flanking region of the albumin and alpha-fetoprotein (Afp) genes in different developing rat tissues and cloned cell lines that display various functional states of these genes. Nuclease-hypersensitive sites were probed with DNase I, using an indirect end-labeling technique. In albumin-producing rat cells two major DNase I-hypersensitive sites were found near the promoter region and one additional site was located approximately 3 kilobases (kb) upstream. Similarly, in Afp-producing rat tissues and cell lines we mapped one DNase I-hypersensitive region close to the promoter region and two cleavage sites further upstream at approximately 2.2 and approximately 3.8 kb from the cap site. The DNase I-hypersensitive sites of both genes were absent in nonhepatic rat cells and therefore appear to be tissue specific. Loss of specific sets of DNase I-hypersensitive sites accompanies the cessation of transcription for the Afp gene in adult rat liver and in a "dedifferentiated" hepatoma cell line. Likewise, specific sets of DNase I-hypersensitive sites disappear during the inactivation of the albumin gene in hepatoma cells. The distal upstream sites of the Afp and albumin genes display the same DNase I sensitivity in expressing and potentially expressible states. These findings suggest that reversible changes in short chromatin regions may be involved in the actual transcription of the albumin and Afp genes, while more permanent tissue-specific changes at other sites correlate with the capacity of these genes to be expressed during hepatic differentiation and neoplasia.
