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Updated: Jul 13, 2026

A Non-random Mouse Model for Pharmacological Reactivation of Mecp2 on the Inactive X Chromosome
Published on: May 22, 2019
Cotranscriptional recruitment of the dosage compensation complex to X-linked target genes
1European Molecular Biology Laboratory, Heidelberg 69117, Germany.
Abstract:
Dosage compensation is a process required to balance the expression of X-linked genes between males and females. In Drosophila this is achieved by targeting the dosage compensation complex or the male-specific lethal (MSL) complex to the male X chromosome. In order to study the mechanism of targeting, we have studied two X-chromosomal genes, mof and CG3016, using chromatin immunoprecipitation as well as immuno-FISH analysis on transgenic flies. We show that MSL complex recruitment requires the genes to be in a transcriptionally active state. MSL complex recruitment is reversible because blocking transcription severely reduces MSL binding to its target genes. Furthermore, targeting cues are found toward the 3' end of the gene and depend on the passage of the transcription machinery through the gene, whereby the type of promoter and the direction of transcription are dispensable. We propose a model of dynamic MSL complex binding to active genes based on exposed DNA target elements.
Insights
Dosage compensation in Drosophila relies on the male-specific lethal (MSL) complex targeting active X-linked genes. MSL complex recruitment is reversible and depends on transcription, with targeting cues located at the gene
Area of Science:
- Genetics
- Molecular Biology
- Chromosomal Biology
Background:
- Dosage compensation balances X-linked gene expression between sexes.
- In Drosophila, the male-specific lethal (MSL) complex targets the male X chromosome for this process.
- Understanding MSL complex targeting mechanisms is crucial for comprehending gene regulation.
Purpose of the Study:
- To investigate the mechanism of MSL complex targeting to X-chromosomal genes.
- To determine the relationship between gene transcription and MSL complex recruitment.
- To identify the location and dependencies of targeting cues.
Main Methods:
- Chromatin immunoprecipitation (ChIP) on transgenic Drosophila.
- Immuno-fluorescence in situ hybridization (immuno-FISH) analysis.
- Analysis of specific X-chromosomal genes (mof and CG3016).
Main Results:
- MSL complex recruitment is dependent on the transcriptional activity of X-linked genes.
- MSL complex binding is reversible, decreasing significantly upon blocking transcription.
- Targeting cues are located towards the 3' end of genes and rely on transcription machinery passage.
Conclusions:
- Gene transcription is essential for MSL complex targeting to the X chromosome.
- The dynamic binding of the MSL complex is influenced by transcription-dependent exposed DNA elements.
- A model for dynamic MSL complex binding to active genes is proposed.
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