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：2004
卷号：101
期号：18
页码：7028-7033
DOI：10.1073/pnas.0307985101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The mammalian {beta}-globin loci each contain a family of developmentally expressed genes, and a far upstream regulatory element, the locus control region (LCR). In adult murine erythroid cells, the LCR and the transcribed {beta}-globin genes exist within domains of histone acetylation and RNA polymerase II (pol II) is associated with them. In contrast, the silent embryonic genes lie between these domains within hypoacetylated chromatin, and pol II is not found there. We used chromatin immunoprecipitation and real-time PCR to analyze histone modification and pol II recruitment to the globin locus in human erythroid K562 cells that express the embryonic {epsilon}-globin gene but not the adult {beta}-globin gene. H3 and H4 acetylation and H3 K4 methylation were continuous over a 17-kb region including the LCR and the active {epsilon}-globin gene. The level of modification varied directly with the transcription of the {epsilon}-globin gene. In contrast, this region in nonerythroid HeLa cells lacked these modifications and displayed instead widespread H3 K9 methylation. pol II was also detected continuously from the LCR to the {epsilon}-globin gene. These studies reveal several aspects of chromatin structure and pol II distribution that distinguish the globin locus at embryonic and adult stages and suggest that both enhancer looping and tracking mechanisms may contribute to LCR-promoter communication at different developmental stages.
