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Diverse histone modifications on histone 3 lysine 9 and their relation to DNA methylation in specifying gene silencing.
- Source :
-
BMC genomics [BMC Genomics] 2007 May 24; Vol. 8, pp. 131. Date of Electronic Publication: 2007 May 24. - Publication Year :
- 2007
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Abstract
- Background: Previous studies of individual genes have shown that in a self-enforcing way, dimethylation at histone 3 lysine 9 (dimethyl-H3K9) and DNA methylation cooperate to maintain a repressive mode of inactive genes. Less clear is whether this cooperation is generalized in mammalian genomes, such as mouse genome. Here we use epigenomic tools to simultaneously interrogate chromatin modifications and DNA methylation in a mouse leukemia cell line, L1210.<br />Results: Histone modifications on H3K9 and DNA methylation in L1210 were profiled by both global CpG island array and custom mouse promoter array analysis. We used chromatin immunoprecipitation microarray (ChIP-chip) to examine acetyl-H3K9 and dimethyl-H3K9. We found that the relative level of acetyl-H3K9 at different chromatin positions has a wider range of distribution than that of dimethyl-H3K9. We then used differential methylation hybridization (DMH) and the restriction landmark genome scanning (RLGS) to analyze the DNA methylation status of the same targets investigated by ChIP-chip. The results of epigenomic profiling, which have been independently confirmed for individual loci, show an inverse relationship between DNA methylation and histone acetylation in regulating gene silencing. In contrast to the previous notion, dimethyl-H3K9 seems to be less distinct in specifying silencing for the genes tested.<br />Conclusion: This study demonstrates in L1210 leukemia cells a diverse relationship between histone modifications and DNA methylation in the maintenance of gene silencing. Acetyl-H3K9 shows an inverse relationship between DNA methylation and histone acetylation in regulating gene silencing as expected. However, dimethyl-H3K9 seems to be less distinct in relation to promoter methylation. Meanwhile, a combination of epigenomic tools is of help in understanding the heterogeneity of epigenetic regulation, which may further our vision accumulated from single-gene studies.
- Subjects :
- Acetylation
Animals
Azacitidine analogs & derivatives
Azacitidine pharmacology
Cell Line, Tumor
Chromatin Immunoprecipitation
CpG Islands genetics
DNA Modification Methylases antagonists & inhibitors
Decitabine
Gene Expression Regulation drug effects
Hydroxamic Acids pharmacology
Leukemia L1210 genetics
Leukemia L1210 metabolism
Leukemia L1210 pathology
Lysine metabolism
Methylation
Mice
Mice, Inbred DBA
Oligonucleotide Array Sequence Analysis
DNA Methylation
Gene Silencing
Histones metabolism
Protein Processing, Post-Translational
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2164
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- BMC genomics
- Publication Type :
- Academic Journal
- Accession number :
- 17524140
- Full Text :
- https://doi.org/10.1186/1471-2164-8-131