The chromosomal high-affinity binding sites for the Drosophila dosage compensation complex

Dosage compensation in male Drosophila relies on the X chromosome-specific recruitment of a chromatin-modifying machinery, the dosage compensation complex (DCC). The principles that assure selective targeting of the DCC are unknown. According to a prevalent model, X chromosome targeting is initiated...

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Bibliographic Details
Published in:PLoS genetics 2008-12, Vol.4 (12), p.e1000302-e1000302
Main Authors: Straub, Tobias, Grimaud, Charlotte, Gilfillan, Gregor D, Mitterweger, Angelika, Becker, Peter B
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Cell Biology/Gene Expression
Cell Biology/Nuclear Structure and Function
Cell Line
Chromatin
Chromosome Mapping
Chromosomes
Compensation
Deoxyribonucleic acid
DNA
DNA methylation
Dosage Compensation, Genetic
Drosophila
Drosophila - chemistry
Drosophila - genetics
Experiments
Female
Genetics
Genetics and Genomics/Chromosome Biology
Genetics and Genomics/Epigenetics
Genetics and Genomics/Genomics
Genomes
Male
Molecular Biology/Chromatin Structure
Molecular Biology/Chromosome Structure
Principles
Proteins
Sex Chromosomes - chemistry
Sex Chromosomes - genetics
Untranslated Regions
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Summary:Dosage compensation in male Drosophila relies on the X chromosome-specific recruitment of a chromatin-modifying machinery, the dosage compensation complex (DCC). The principles that assure selective targeting of the DCC are unknown. According to a prevalent model, X chromosome targeting is initiated by recruitment of the DCC core components, MSL1 and MSL2, to a limited number of so-called "high-affinity sites" (HAS). Only very few such sites are known at the DNA sequence level, which has precluded the definition of DCC targeting principles. Combining RNA interference against DCC subunits, limited crosslinking, and chromatin immunoprecipitation coupled to probing high-resolution DNA microarrays, we identified a set of 131 HAS for MSL1 and MSL2 and confirmed their properties by various means. The HAS sites are distributed all over the X chromosome and are functionally important, since the extent of dosage compensation of a given gene and its proximity to a HAS are positively correlated. The sites are mainly located on non-coding parts of genes and predominantly map to regions that are devoid of nucleosomes. In contrast, the bulk of DCC binding is in coding regions and is marked by histone H3K36 methylation. Within the HAS, repetitive DNA sequences mainly based on GA and CA dinucleotides are enriched. Interestingly, DCC subcomplexes bind a small number of autosomal locations with similar features.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1000302