Role for DNA methylation in the control of cell type–specific maspin expression
- 20 May 2002
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 31 (2), 175-179
- https://doi.org/10.1038/ng886
Abstract
The nucleotide 5-methylcytosine is involved in processes crucial in mammalian development, such as X-chromosome inactivation and gene imprinting1,2,3,4,5. In addition, cytosine methylation has long been speculated to be involved in the establishment and maintenance of cell type–specific expression of developmentally regulated genes6,7; however, it has been difficult to identify clear examples of such genes, particularly in humans8. Here we provide evidence that cytosine methylation of the maspin gene (SERPINB5) promoter controls, in part, normal cell type–specific SERPINB5 expression. In normal cells expressing SERPINB5, the SERPINB5 promoter is unmethylated and the promoter region has acetylated histones and an accessible chromatin structure. By contrast, normal cells that do not express SERPINB5 have a completely methylated SERPINB5 promoter with hypoacetylated histones, an inaccessible chromatin structure and a transcriptional repression that is relieved by inhibition of DNA methylation. These findings indicate that cytosine methylation is important in the establishment and maintenance of cell type–restricted gene expression.Keywords
This publication has 31 references indexed in Scilit:
- How Are Alkynes Scrambled?Science, 2005
- Differential DNA methylation of the p16 INK4A/CDKN2A promoter in human oral cancer cells and normal human oral keratinocytesOral Oncology, 1999
- Loss of methylation activates Xist in somatic but not in embryonic cells.Genes & Development, 1995
- Maspin, a Serpin with Tumor-Suppressing Activity in Human Mammary Epithelial CellsScience, 1994
- Role for DNA methylation in genomic imprintingNature, 1993
- CpG islands as gene markers in the human genomeGenomics, 1992
- Targeted mutation of the DNA methyltransferase gene results in embryonic lethalityCell, 1992
- CpG Islands in vertebrate genomesJournal of Molecular Biology, 1987
- MAMMALIAN X-CHROMOSOME INACTIVATIONAnnual Review of Genetics, 1983
- X inactivation, differentiation, and DNA methylationCytogenetic and Genome Research, 1975