Transcription modulation chromosome-wide: universal features and principles of dosage compensation in worms and flies

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Dosage compensation processes in flies and worms provide a unique opportunity to study common regulatory principles of thousands of genes. Technological advancement in the recent years has allowed for the comprehensive description of key aspects such as the targeting of the regulatory factors, the emerging chromatin structure changes and the ensuing subtle transcriptional alterations. With plenty of data at hand the challenge remains to integrate the findings into coherent models that appreciate the global nature of the underlying principles leaving the experimental anecdotes behind while avoiding the numerical burlesque.

Section snippets

Introduction: dosage compensation in worms and flies

Chromosome-wide dosage compensation (DC) occurs in several organisms, particularly in those in which the males are heterogametic and carry one X chromosome (the females have two X chromosomes). The compensation process assures that gene expression from the single copy X chromosome is balanced with the expression of the diploid autosomes. This global adjustment is not a universal requirement as, for example, birds and lepidoptera have not evolved a systematic, genome-wide process but rather

Choice and coating of the right chromosome

An intriguing aspect of DC complexes is their ability to specifically recognize the sex chromosomes. The association with large parts of the X chromosomes in either fly or worm follows a two-step process: initial binding to a limited set of distinct X-chromosomal loci is followed by dispersion — often referred to as ‘spreading’ — of the complexes in cis to the majority of the steady-state chromosomal binding sites (reviewed in [2, 4, 5]).

In Drosophila, the sites of initial binding (high

Fine-tuning transcription by modulating chromatin structure

Chromatin features are likely to provide input for the faithful recruitment of DCCs and, likewise, for their functional output affecting the transcription machinery indirectly by modulation of chromatin structure. Some chromatin features can be found enriched on all X chromosomes (compensated or not) by comparison to autosomes indicating that the sex chromosomes acquired chromatin features independently of the installation of the DC system [19]. In many cases, the relevance of such enrichments

Chromosome-wide modulation of transcription

The DC processes mediated by the dedicated DC systems cannot be viewed in isolation, but are integrated with additional tuning processes that occur simultaneously. For example, spontaneously arising aneuploidies are thought to trigger an immediate, non-specific feedback response that partially compensates for the deletion of a gene copy (reviewed in [37]). Such a mechanism, may contribute to X chromosomal DC as well. If the dDCC in flies is inactivated, X chromosomal gene expression is reduced,

Open questions

Genomic approaches to studying DC have raised the level of analysis from the anecdotal, single gene level to a global, general level. Several unresolved issues, however, remain. For example, it is completely unknown to which extent post-transcriptional processing of the transcript contributes to DC, as so far only steady-state mRNA levels have been measured [38, 40••]. In addition, it will be of prime interest to determine the precise RNA polymerase output for correlation analyses with

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

Work in the authors’ laboratory on dosage compensation is supported by the Deutsche Forschungsgemeinschaft through SFB-TR5 and the Gottfried-Wilhelm-Leibniz Programme.

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