Molecular landscape of modified histones in Drosophila heterochromatic genes and euchromatin-heterochromatin transition zones
| Autor: | Barbara T. Wakimoto, Jiro C. Yasuhara |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Chromatin Immunoprecipitation Embryo Nonmammalian Euchromatin Retroelements lcsh:QH426-470 Heterochromatin Gene Expression Genes Insect Chromosomal rearrangement Chromosomes Histones 03 medical and health sciences 0302 clinical medicine Genetics Constitutive heterochromatin Animals Drosophila Proteins Gene Silencing Molecular Biology Genetics (clinical) Ecology Evolution Behavior and Systematics Pericentric heterochromatin 030304 developmental biology Oligonucleotide Array Sequence Analysis 0303 health sciences biology Homozygote Genetics and Genomics Histone-Lysine N-Methyltransferase Methyltransferases Protein Structure Tertiary Repressor Proteins lcsh:Genetics Histone Histone methyltransferase biology.protein Heterochromatin protein 1 Drosophila 030217 neurology & neurosurgery Research Article |
| Zdroj: | PLoS Genetics, Vol 4, Iss 1, p e16 (2008) PLoS Genetics |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | Constitutive heterochromatin is enriched in repetitive sequences and histone H3-methylated-at-lysine 9. Both components contribute to heterochromatin's ability to silence euchromatic genes. However, heterochromatin also harbors hundreds of expressed genes in organisms such as Drosophila. Recent studies have provided a detailed picture of sequence organization of D. melanogaster heterochromatin, but how histone modifications are associated with heterochromatic sequences at high resolution has not been described. Here, distributions of modified histones in the vicinity of heterochromatic genes of normal embryos and embryos homozygous for a chromosome rearrangement were characterized using chromatin immunoprecipitation and genome tiling arrays. We found that H3-di-methylated-at-lysine 9 (H3K9me2) was depleted at the 5′ ends but enriched throughout transcribed regions of heterochromatic genes. The profile was distinct from that of euchromatic genes and suggests that heterochromatic genes are integrated into, rather than insulated from, the H3K9me2-enriched domain. Moreover, the profile was only subtly affected by a Su(var)3–9 null mutation, implicating a histone methyltransferase other than SU(VAR)3–9 as responsible for most H3K9me2 associated with heterochromatic genes in embryos. On a chromosomal scale, we observed a sharp transition to the H3K9me2 domain, which coincided with increased retrotransposon density in the euchromatin-heterochromatin (eu-het) transition zones on the long chromosome arms. Thus, a certain density of retrotransposons, rather than specific boundary elements, may demarcate Drosophila pericentric heterochromatin. We also demonstrate that a chromosome rearrangement that created a new eu-het junction altered H3K9me2 distribution and induced new euchromatic sites of enrichment as far as several megabases away from the breakpoint. Taken together, the findings argue against simple classification of H3K9me as the definitive signature of silenced genes, and clarify roles of histone modifications and repetitive DNAs in heterochromatin. The results are also relevant for understanding the effects of chromosome aberrations and the megabase scale over which epigenetic position effects can operate in multicellular organisms. Author Summary The chromosomal domain “heterochromatin” was first defined at the cytological level by its deeply staining appearance compared to more lightly stained domains called “euchromatin.” Abnormal juxtaposition of these two domains by chromosome rearrangements results in silencing of the nearby euchromatic genes. This effect is mediated by heterochromatin-enriched chromosomal proteins and led to the prevalent view of heterochromatin as incompatible with gene expression. Paradoxically, some expressed genes reside within heterochromatin. In this study, we examined how heterochromatic genes fit into a genomic context known for silencing effects. We found that Drosophila heterochromatic genes are integrated into the domain enriched in the modified histone H3K9me2, suggesting that the effect of this protein on gene expression is context-dependent. We also investigated the molecular nature of euchromatin-heterochromatin transition zones in the normal and rearranged chromosomes. The results provide insights into the functions of repetitive DNAs and H3K9me2 in heterochromatin and document the long distance over which a heterochromatic breakpoint can affect the molecular landscape of a chromosomal region. These findings have implications for understanding the consequences of chromosome abnormalities in organisms, including humans. |
| Databáze: | OpenAIRE |
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